2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T4a2,Twenty individuals from 10 families (50% female and 50% male; 70% self-described as broadly European [Australian/British, British, English/German, English/Polish, European, or Scottish], 25% as Asian [Chinese or Filipino], and 5% as Latin American [Salvadoran]) were identified with FOXC1 duplications. All genetically tested individuals were diagnosed with glaucoma, demonstrating high penetrance. Seventeen individuals were referred with juvenile open-angle glaucoma (JOAG), 1 with primary open-angle glaucoma, 1 with primary congenital glaucoma, and 1 with anterior segment dysgenesis. The diagnosis of 4 individuals from 1 family with ectropion uveae was revised to anterior segment dysgenesis. Systemic features were reported for 2 participants (10.5%), including subtle dental findings and mild facial dysmorphism. Duplications encompassing FOXC1 were among the most common monogenic contributors to JOAG. In the ANZRAG group, they accounted for 13.5% (95% CI, 6.7%-25.3%) of JOAG probands with a genetic diagnosis, second to MYOC (53.8%; 95% CI, 40.5%-66.7%). In the MEE group, FOXC1 duplications accounted for 9.5% (95% CI, 2.7%-28.9%) of JOAG probands with a genetic diagnosis.31:Tb02,While FOXC1 single-nucleotide variants and deletions are well-established causes of Axenfeld-Rieger syndrome, few FOXC1 duplications have been reported. This study investigated families with duplications encompassing the FOXC1 gene to refine the associated phenotypic spectrum and contribution to glaucoma. To investigate the prevalence and phenotype of FOXC1 duplications in 2 large glaucoma registries. This retrospective observational genetic cohort study included participants recruited from the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) and the Massachusetts Eye and Ear (MEE) cohort from 2008 through 2025. Participants with glaucoma, and available relatives, underwent genomic testing to identify duplications encompassing FOXC1 using exome sequencing and genotyping arrays (ANZRAG) or whole-genome sequencing (MEE). Data analyses were conducted from 2022 through 2025. Prevalence of FOXC1 duplications, age at glaucoma onset, and phenotype, including ocular and systemic features. Twenty individuals from 10 families (50% female and 50% male; 70% self-described as broadly European [Australian/British, British, English/German, English/Polish, European, or Scottish], 25% as Asian [Chinese or Filipino], and 5% as Latin American [Salvadoran]) were identified with FOXC1 duplications. All genetically tested individuals were diagnosed with glaucoma, demonstrating high penetrance. Seventeen individuals were referred with juvenile open-angle glaucoma (JOAG), 1 with primary open-angle glaucoma, 1 with primary congenital glaucoma, and 1 with anterior segment dysgenesis. The diagnosis of 4 individuals from 1 family with ectropion uveae was revised to anterior segment dysgenesis. Systemic features were reported for 2 participants (10.5%), including subtle dental findings and mild facial dysmorphism. Duplications encompassing FOXC1 were among the most common monogenic contributors to JOAG. In the ANZRAG group, they accounted for 13.5% (95% CI, 6.7%-25.3%) of JOAG probands with a genetic diagnosis, second to MYOC (53.8%; 95% CI, 40.5%-66.7%). In the MEE group, FOXC1 duplications accounted for 9.5% (95% CI, 2.7%-28.9%) of JOAG probands with a genetic diagnosis. These findings suggest FOXC1 duplications are an underrecognized, highly penetrant, but variably expressive, genetic variation associated with JOAG. Findings for the relatively modest number of individuals in the retrospective study were associated with wide confidence intervals. This limitation is often inherent to studies of JOAG, a rare condition for which individual genetic variants account for only a subset of cases. Despite this, the findings highlight the genetic heterogeneity of JOAG and support the potential importance of considering routine genetic copy-number variant analysis for individuals with JOAG.32:T13da, Importance While FOXC1 single-nucleotide variants and deletions are well-established causes of Axenfeld-Rieger syndrome, few FOXC1 duplications have been reported. This study investigated families with duplications encompassing the FOXC1 gene to refine the associated phenotypic spectrum and contribution to glaucoma. Objective To investigate the prevalence and phenotype of FOXC1 duplications in 2 large glaucoma registries. Design, Setting, and Participants This retrospective observational genetic cohort study included participants recruited from the Australian &amp; New Zealand Registry of Advanced Glaucoma (ANZRAG) and the Massachusetts Eye and Ear (MEE) cohort from 2008 through 2025. Participants with glaucoma, and available relatives, underwent genomic testing to identify duplications encompassing FOXC1 using exome sequencing and genotyping arrays (ANZRAG) or whole-genome sequencing (MEE). Data analyses were conducted from 2022 through 2025. Main Outcomes and Measures Prevalence of FOXC1 duplications, age at glaucoma onset, and phenotype, including ocular and systemic features. Results Twenty individuals from 10 families (50% female and 50% male; 70% self-described as broadly European [Australian/British, British, English/German, English/Polish, European, or Scottish], 25% as Asian [Chinese or Filipino], and 5% as Latin American [Salvadoran]) were identified with FOXC1 duplications. All genetically tested individuals were diagnosed with glaucoma, demonstrating high penetrance. Seventeen individuals were referred with juvenile open-angle glaucoma (JOAG), 1 with primary open-angle glaucoma, 1 with primary congenital glaucoma, and 1 with anterior segment dysgenesis. The diagnosis of 4 individuals from 1 family with ectropion uveae was revised to anterior segment dysgenesis. Systemic features were reported for 2 participants (10.5%), including subtle dental findings and mild facial dysmorphism. Duplications encompassing FOXC1 were among the most common monogenic contributors to JOAG. In the ANZRAG group, they accounted for 13.5% (95% CI, 6.7%-25.3%) of JOAG probands with a genetic diagnosis, second to MYOC (53.8%; 95% CI, 40.5%-66.7%). In the MEE group, FOXC1 duplications accounted for 9.5% (95% CI, 2.7%-28.9%) of JOAG probands with a genetic diagnosis. Conclusions and Relevance These findings suggest FOXC1 duplications are an underrecognized, highly penetrant, but variably expressive, genetic variation associated with JOAG. Findings for the relatively modest number of individuals in the retrospective study were associated with wide confidence intervals. This limitation is often inherent to studies of JOAG, a rare condition for which individual genetic variants account for only a subset of cases. Despite this, the findings highlight the genetic heterogeneity of JOAG and support the potential importance of considering routine genetic copy-number variant analysis for individuals with JOAG. 33:T66b,Inherited Retinal Disorders (IRDs) are a leading cause of blindness in working age adults. With the emergence of therapeutic approaches and pre-implantation genetic testing, obtaining a molecular diagnosis is increasingly important. As such we aimed to determine the caseload of IRD patients presenting to Scottish ophthalmology services over a 5-year period, and evaluated the diagnostic approaches used and results of genetic testing in order to determine any established inherited cause. Data from all patients presenting to ophthalmology services across Scotland from January 2018 to January 2023 diagnosed with an IRD were collected. History and examination findings were recorded, as were the methods of genetic testing used, the identified genetic variants and the time taken for molecular reporting. 532 patients were included in the analysis. The most common clinical diagnosis was retinitis pigmentosa (RP) (42.4%), followed by Stargardt Disease (9.0%), with Usher syndrome the most common syndromic RP. The most common initial test was a 176 gene panel, followed by direct testing for ABCA4, with different regions pursuing different testing strategies. 67.4% of patients received a molecular diagnosis. The most common causal gene was ABCA4, followed by USH2A and RDS/PRPH2. This study provides the first assessment of IRDs in Scotland over a 5 year period. We demonstrate that the most common clinical diagnoses are RP and Stargardt disease, and that the majority received a molecular diagnosis. This work provides a unique insight into the Scottish ophthalmic genetics service and serves as a benchmark for iterative improvement.34:T8e7,Abstract Objective Inherited Retinal Disorders (IRDs) are a leading cause of blindness in working age adults. With the emergence of therapeutic approaches and pre-implantation genetic testing, obtaining a molecular diagnosis is increasingly important. As such we aimed to determine the caseload of IRD patients presenting to Scottish ophthalmology services over a 5-year period, and evaluated the diagnostic approaches used and results of genetic testing in order to determine any established inherited cause. Subjects Data from all patients presenting to ophthalmology services across Scotland from January 2018 to January 2023 diagnosed with an IRD were collected. History and examination findings were recorded, as were the methods of genetic testing used, the identified genetic variants and the time taken for molecular reporting. Results 532 patients were included in the analysis. The most common clinical diagnosis was retinitis pigmentosa (RP) (42.4%), followed by Stargardt Disease (9.0%), with Usher syndrome the most common syndromic RP. The most common initial test was a 176 gene panel, followed by direct testing for ABCA4, with different regions pursuing different testing strategies. 67.4% of patients received a molecular diagnosis. The most common causal gene was ABCA4, followed by USH2A and RDS/PRPH2. Conclusion This study provides the first assessment of IRDs in Scotland over a 5 year period. We demonstrate that the most common clinical diagnoses are RP and Stargardt disease, and that the majority received a molecular diagnosis. This work provides a unique insight into the Scottish ophthalmic genetics service and serves as a benchmark for iterative improvement. 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Genetic Testing: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Genetic Testing (modality). Clinician-written summaries and actionable practice insights. 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the sample_size tag reflects families, not individual participants.","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2026.3828","tag_type":"warning","value":"Sample size is very small (3 families with the p.Arg140Trp variant); findings should be interpreted as hypothesis-generating, not definitive.","value_numeric":null},{"paper_doi":"10.1001/jamaophthalmol.2026.3828","tag_type":"warning","value":"The comparator 'family' with canonical DHRD/ML appears to consist of a single patient, not a full family cohort, limiting direct comparison.","value_numeric":null}],"summaries":{"what_studied":"This multi-institutional case series evaluated the clinical and functional phenotype of the *EFEMP1* p.Arg140Trp (c.418C>T) variant in 3 unrelated families with inherited retinal degeneration, compared against a family with canonical Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML) caused by p.Arg345Trp, using multimodal imaging and rod-mediated dark adaptation testing (October 1998–May 2026).","key_result":"The p.Arg140Trp variant segregated with disease in all 3 families, producing a **late-onset, predominantly peripheral retinal degeneration** distinct from DHRD/ML: 4 of 5 at-risk heterozygous relatives (ages 50–58) showed delayed rod-mediated dark adaptation despite 20/20 visual acuity and normal fundus appearance, while symptomatic carriers from families 2 and 3 had nyctalopia and peripheral chorioretinal atrophy (initially misclassified as gyrate atrophy-like or choroideremia-like); rod dysfunction was most severe toward the periphery (15°, 30°, 46°), with dysfunction present even at retinal loci lacking detectable outer nuclear layer loss.","limitations":"- Very small sample (3 families, limited number of affected individuals), limiting generalizability.\n- No longitudinal functional data to characterize disease progression rate.\n- Rod dysfunction was detected at structurally normal loci, but no histopathologic or molecular mechanistic data are provided to explain the dissociation.","practice_takeaway":"Clinicians should consider *EFEMP1* variants beyond p.Arg345Trp when evaluating late-onset peripheral retinal degeneration with nyctalopia, especially cases resembling gyrate atrophy or choroideremia. Rod-mediated dark adaptation testing may detect early functional loss before structural changes appear on imaging."}},{"doi":"10.1161/circulationaha.126.080608","pmid":"42708210","title":"Arrhythmic Risk Stratification According to LGE Corridors and Genetics in Nonischemic Dilated Cardiomyopathy","journal_title":"Circulation","journal_issn":"0009-7322","published_at":"2026-09-08T00:00:00.000Z","url":"https://doi.org/10.1161/circulationaha.126.080608","source_score":38,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-12T06:20:14.135Z","updated_at":"2026-09-12T06:20:14.135Z","tags":[{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"condition","value":"Nonischemic Dilated Cardiomyopathy","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"condition","value":"Ventricular Arrhythmia","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"modality","value":"Cardiac Magnetic Resonance Imaging","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"sample_size","value":"n=925","value_numeric":925},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"study_design","value":"Prospective Multicenter Cohort Study","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"warning","value":"High-risk genotype definitions and the specific genes included are not detailed in the abstract; clinical applicability depends on the genetic panel used.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"warning","value":"'LGE corridor' quantification is a specialized post-processing technique not yet widely available in routine clinical CMR workflows.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080608","tag_type":"warning","value":"The study is described as enrolling 'consecutive patients' but the design is retrospective in nature — the label 'prospective cohort' is inferred from multicenter enrollment language; clinicians should verify the exact study design in the full text.","value_numeric":null}],"summaries":{"what_studied":"This multicenter European cohort study (22 centers, n=925) evaluated whether LGE conduction corridors on cardiac MRI and high-risk genotypes (HRGs) independently predict major ventricular arrhythmic events (MVAs) in nonischemic dilated cardiomyopathy (NIDCM), compared with the guideline-standard LVEF ≤35% threshold, over a median follow-up of 5.4 years.","key_result":"LGE corridors (SHR 1.25 per corridor, 95% CI 1.11–1.42; P<0.001) and HRGs (SHR 2.28, 95% CI 1.32–3.96; P=0.003) independently predicted MVA. A stepwise algorithm combining LGE presence, ≥4 LGE corridors, and HRG achieved a 5-year AUC of 0.72 vs. 0.57 for LVEF ≤35% alone (P=0.001); 10.3% of patients (95/925) experienced an MVA.","limitations":"Retrospective multicenter cohort design limits causal inference; LGE corridor analysis requires specialized post-processing expertise not yet standardized across centers; genotyping panel scope and variant classification criteria may vary across the 22 sites.","practice_takeaway":"For patients with NIDCM, combining CMR-derived LGE corridors (≥4 as the key cutoff) with genetic high-risk status substantially improves arrhythmic risk classification beyond LVEF alone. Clinicians should consider integrating cardiac MRI fibrosis characterization and genetic testing into ICD decision-making, rather than relying solely on LVEF ≤35%."}},{"doi":"10.1001/jamadermatol.2026.3186","pmid":"42684697","title":"Acantholytic Blistering of the Oroesophageal Mucosa Due to Homozygous\n DSG3\n Pathogenic Missense Variant","journal_title":"JAMA Dermatology","journal_issn":"2168-6068","published_at":"2026-09-02T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13539445/","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-08T06:31:51.666Z","updated_at":"2026-09-08T06:31:51.666Z","tags":[{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"age_group","value":"neonate","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"condition","value":"Acantholytic Blistering","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"condition","value":"Pemphigus","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"study_design","value":"Genetic Association Study","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"warning","value":"Full text is under embargo until September 2, 2027; all structured data is derived solely from the abstract and publisher page. Key details such as sample size, clinical outcomes, and treatment data are not verifiable.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"warning","value":"Level of evidence set to 4 (case study/small series) based on context, but could not be confirmed from full text.","value_numeric":null},{"paper_doi":"10.1001/jamadermatol.2026.3186","tag_type":"warning","value":"The study design label 'Genetic Association Study' is taken directly from the abstract; the study may be a case report or case series given the context of re-examining a prior single case report.","value_numeric":null}],"summaries":{"what_studied":"This genetic association study re-examined a prior case report originally diagnosed as persistent neonatal pemphigus, evaluating whether the condition was autoimmune or genetic in origin, specifically investigating a homozygous pathogenic missense variant in *DSG3* (desmoglein-3) as the cause of acantholytic blistering of the oroesophageal mucosa.","key_result":"The study reclassified the prior case of persistent neonatal pemphigus as genetic rather than autoimmune in origin, attributing the oroesophageal acantholytic blistering to a homozygous *DSG3* pathogenic missense variant.","limitations":"Only an abstract is publicly available due to a publication embargo; full text is not accessible until September 2027. Sample size and detailed clinical data cannot be assessed. Study appears limited to a single case or very small cohort, restricting generalizability.","practice_takeaway":"In neonates or infants presenting with persistent mucosal blistering resembling pemphigus, consider genetic testing for *DSG3* variants before attributing disease to autoimmune mechanisms. A genetic etiology has fundamentally different treatment and counseling implications than autoimmune pemphigus."}},{"doi":"10.1016/j.jaad.2026.08.039","pmid":"42607952","title":"Low Prevalence of Hereditary Melanoma Among Patients Referred for Genetic Testing: A Multicentre Retrospective Cohort Study","journal_title":"Journal of the American Academy of Dermatology","journal_issn":"0190-9622","published_at":"2026-08-17T00:00:00.000Z","url":"https://doi.org/10.1016/j.jaad.2026.08.039","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-28T06:25:20.373Z","updated_at":"2026-08-28T06:25:20.373Z","tags":[{"paper_doi":"10.1016/j.jaad.2026.08.039","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.039","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.039","tag_type":"condition","value":"Hereditary Melanoma","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.039","tag_type":"condition","value":"Melanoma","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.039","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.039","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.039","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.039","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.039","tag_type":"warning","value":"Study design classified as 'Retrospective Cohort Study' based on the title descriptor; no abstract or methods were available to confirm.","value_numeric":null},{"paper_doi":"10.1016/j.jaad.2026.08.039","tag_type":"warning","value":"The full text of this paper was not provided — only the title, journal, DOI, and publication date were supplied. All summary content and tags are inferred from the title alone. Specific numeric results, sample size, gene panel details, sex distribution, and patient demographics could not be extracted. Treat all summary details as provisional until the full text is reviewed.","value_numeric":null}],"summaries":{"limitations":"Retrospective design limits causal inference; referral bias may overestimate yield compared to unselected populations; specific gene panel compositions and referral criteria may vary across centres.","key_result":"The study found a low prevalence of hereditary melanoma among referred patients, though specific numeric results (e.g., exact yield percentages or variant counts) are not available from the provided source text.","what_studied":"This multicentre retrospective cohort study evaluated the prevalence of hereditary melanoma among patients referred for genetic testing, examining how often a pathogenic or likely pathogenic variant was identified in melanoma-predisposition genes.","practice_takeaway":"Clinicians should be aware that even among patients referred for genetic testing for melanoma, the yield of actionable hereditary variants is low. This suggests a need for refined referral criteria to improve the efficiency of genetic testing programs."}},{"doi":"10.1016/s1474-4422(26)00198-5","pmid":"42456684","title":"Parkinson's disease genetics across diverse ancestries: an observational genetic study of causal and risk variants with translational implications","journal_title":"The Lancet Neurology","journal_issn":"1474-4422","published_at":"2026-07-16T00:00:00.000Z","url":"https://doi.org/10.1016/s1474-4422(26)00198-5","source_score":55,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-24T13:38:09.408Z","updated_at":"2026-07-24T13:38:09.408Z","tags":[{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"condition","value":"Parkinsonism","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"condition","value":"Parkinson's Disease","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"generic","value":"GBA1 variant","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"generic","value":"LRRK2 variant","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"generic","value":"PRKN variant","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"modality","value":"Exome Sequencing","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"modality","value":"Genome Sequencing","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"sample_size","value":"n=99783","value_numeric":99783},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"study_design","value":"Observational Cross-Sectional Genetic Study","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"warning","value":"Age data and sex breakdown by ancestry group are not reported in the abstract; tags reflect the likely adult population but could not be verified at the subgroup level.","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"warning","value":"The 'impact_flag' of practice_changing reflects the scale and diversity of the genetic findings, but direct clinical translation depends on genotyping infrastructure availability, which varies widely.","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00198-5","tag_type":"warning","value":"The study is observational and cross-sectional; variant-disease associations are descriptive and do not establish causality or penetrance estimates by ancestry.","value_numeric":null}],"summaries":{"what_studied":"This multi-ancestry, cross-sectional genetic study characterised the distribution of causal and risk variants in 18 Parkinson's disease-associated genes across 99,783 individuals (58,559 with Parkinson's disease, 41,224 controls) from 11 genetically inferred ancestries, using data from the Global Parkinson's Genetics Program (GP2) release 11.","key_result":"Causal variants were found in 2.1% of PD cases overall, ranging from 0.4% in African to 10.7% in Ashkenazi Jewish ancestry. GBA1 risk variants appeared in 4.1% (east Asian) to 52.9% (African) of PD cases; LRRK2 causal variants peaked in Ashkenazi Jewish (10.7%) and Middle Eastern (4.4%) groups; PRKN biallelic causal variants were highest in Middle Eastern ancestry (1.3%).","limitations":"- ~71% of PD cases were of European or Ashkenazi Jewish ancestry, limiting statistical power for under-represented groups.\n- Cross-sectional, observational design precludes causal or longitudinal inference.\n- Healthy controls were not genetically matched at variant level, and ascertainment methods varied across contributing cohorts.","practice_takeaway":"Genetic testing for PD risk and causal variants should account for ancestry-specific variant spectra — particularly GBA1 in African and LRRK2 in Ashkenazi Jewish and Middle Eastern patients. As GBA1- and LRRK2-targeted trials expand, recruiting ancestrally diverse participants is essential to ensure findings apply broadly."}},{"doi":"10.1111/pai.70440","pmid":"42458766","title":"NFKB2\n mutation as a rare cause of disseminated molluscum contagiosum in a child","journal_title":"Pediatric Allergy and Immunology","journal_issn":"0905-6157","published_at":"2026-07-15T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13373328/","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-22T13:37:47.000Z","updated_at":"2026-07-22T13:37:47.000Z","tags":[{"paper_doi":"10.1111/pai.70440","tag_type":"age_group","value":"child","value_numeric":null},{"paper_doi":"10.1111/pai.70440","tag_type":"category","value":"Allergy","value_numeric":null},{"paper_doi":"10.1111/pai.70440","tag_type":"condition","value":"Disseminated Molluscum Contagiosum","value_numeric":null},{"paper_doi":"10.1111/pai.70440","tag_type":"condition","value":"Primary Immunodeficiency","value_numeric":null},{"paper_doi":"10.1111/pai.70440","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/pai.70440","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1111/pai.70440","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1111/pai.70440","tag_type":"sample_size","value":"n=1","value_numeric":1},{"paper_doi":"10.1111/pai.70440","tag_type":"study_design","value":"Case Report","value_numeric":null},{"paper_doi":"10.1111/pai.70440","tag_type":"warning","value":"Full text was not directly provided; summary is based on the title, journal, and DOI metadata only. Specific clinical details, immunologic workup findings, and treatment outcomes are not verifiable from the available information.","value_numeric":null},{"paper_doi":"10.1111/pai.70440","tag_type":"warning","value":"The exact NFKB2 variant type (gain-of-function vs. loss-of-function) and associated immunophenotype cannot be confirmed without access to the full paper.","value_numeric":null}],"summaries":{"what_studied":"A case report evaluating an NFKB2 mutation as a rare genetic cause of disseminated molluscum contagiosum in a pediatric patient, likely in the context of an underlying primary immunodeficiency.","key_result":"An NFKB2 mutation was identified as the causative genetic defect underlying disseminated molluscum contagiosum in a child, highlighting a novel association between this mutation and susceptibility to this typically self-limited poxvirus infection.","limitations":"Single case report limits generalizability; causal inference is inherently limited without functional immunologic validation or additional cases.","practice_takeaway":"In children with unusually severe or disseminated molluscum contagiosum, consider genetic workup for primary immunodeficiency, including NFKB2 pathway variants. Early identification may guide immunologic management and surveillance for other infections."}},{"doi":"10.1111/pcmr.70091","pmid":"42415511","title":"Copying the Risk: Rise of Phenocopies in\n CDKN2A\n Spanish Families","journal_title":"Pigment Cell & Melanoma Research","journal_issn":"1755-1471","published_at":"2026-07-07T00:00:00.000Z","url":"https://doi.org/10.1111/pcmr.70091","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-17T13:24:19.318Z","updated_at":"2026-07-17T13:24:19.318Z","tags":[{"paper_doi":"10.1111/pcmr.70091","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/pcmr.70091","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1111/pcmr.70091","tag_type":"condition","value":"CDKN2A-Associated Tumor Syndrome","value_numeric":null},{"paper_doi":"10.1111/pcmr.70091","tag_type":"condition","value":"Familial Melanoma","value_numeric":null},{"paper_doi":"10.1111/pcmr.70091","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/pcmr.70091","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1111/pcmr.70091","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1111/pcmr.70091","tag_type":"study_design","value":"Observational Study","value_numeric":null},{"paper_doi":"10.1111/pcmr.70091","tag_type":"warning","value":"Only the paper metadata (title, DOI, journal, date) was provided — no abstract or full text was available. All summary content is inferred from the title alone and should be interpreted with caution. Key quantitative findings, sample size, and study design details could not be verified.","value_numeric":null},{"paper_doi":"10.1111/pcmr.70091","tag_type":"warning","value":"Study design tag and level of evidence are best-guess estimates based on the likely nature of a family-based genetic epidemiology study; actual design may differ.","value_numeric":null}],"summaries":{"what_studied":"This study examined phenocopies — individuals in CDKN2A-positive Spanish melanoma families who develop melanoma without carrying the familial CDKN2A pathogenic variant — to characterize their prevalence and potential drivers.","limitations":"Full text was not available for extraction; specific sample sizes, phenocopy rates, and outcome data could not be confirmed from the abstract alone.","practice_takeaway":"Clinicians managing CDKN2A melanoma families should be aware that non-carriers can still develop melanoma, which may complicate genetic counseling and risk stratification in affected kindreds."}},{"doi":"10.1093/ajrccm/aamag320","pmid":"42412512","title":"From Idiopathic Pulmonary Hemosiderosis to ENaC Channelopathy: A Novel\n SCNN1G\n Mutation","journal_title":"American Journal of Respiratory and Critical Care Medicine","journal_issn":"1073-449X","published_at":"2026-07-07T00:00:00.000Z","url":"https://doi.org/10.1093/ajrccm/aamag320","source_score":3,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-12T13:19:43.122Z","updated_at":"2026-07-12T13:19:43.122Z","tags":[{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"condition","value":"ENaC Channelopathy","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"condition","value":"Idiopathic Pulmonary Hemosiderosis","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"sample_size","value":"n=1","value_numeric":1},{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"study_design","value":"Case Report","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"warning","value":"Age group and sex of the patient are not determinable from the provided metadata and have been omitted.","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"warning","value":"Full text was not available — summary is based solely on title, journal, DOI metadata, and clinical context; specific patient demographics, variant details, and functional data could not be confirmed.","value_numeric":null},{"paper_doi":"10.1093/ajrccm/aamag320","tag_type":"warning","value":"Study design is inferred as a case report from the title and context; this could not be verified without full text access.","value_numeric":null}],"summaries":{"what_studied":"This case report describes a patient initially diagnosed with idiopathic pulmonary hemosiderosis (IPH) who was found to carry a novel mutation in *SCNN1G*, the gene encoding the γ-subunit of the epithelial sodium channel (ENaC), reframing the diagnosis as an ENaC channelopathy.","key_result":"A novel *SCNN1G* mutation was identified as the likely underlying cause of pulmonary hemosiderosis in this patient, suggesting that at least some cases of 'idiopathic' pulmonary hemosiderosis may have a monogenic channelopathy basis.","limitations":"Single case report limits generalizability; functional validation of the specific *SCNN1G* variant's pathogenicity is not described in the abstract; causal relationship between ENaC dysfunction and pulmonary hemorrhage remains to be fully established.","practice_takeaway":"In patients with pulmonary hemosiderosis labeled as idiopathic, consider genetic testing for ENaC subunit mutations (*SCNN1A*, *SCNN1B*, *SCNN1G*), as a channelopathy diagnosis may alter management and counseling. Early genetic workup could prevent prolonged diagnostic uncertainty in similar cases."}},{"doi":"10.1002/art.70257","pmid":"42328836","title":"From Interferon Signature to the Clinical Landscape: Type I Interferonopathies","journal_title":"Arthritis & Rheumatology","journal_issn":"2326-5191","published_at":"2026-06-22T00:00:00.000Z","url":"https://doi.org/10.1002/art.70257","source_score":5,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-27T13:27:35.341Z","updated_at":"2026-06-27T13:27:35.341Z","tags":[{"paper_doi":"10.1002/art.70257","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"condition","value":"Type I Interferonopathy","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"modality","value":"Molecular Diagnostics","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"sample_size","value":"n=46","value_numeric":46},{"paper_doi":"10.1002/art.70257","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"study_design","value":"Observational Cohort Study","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"warning","value":"Age group breakdown is not specified in the abstract — 'mixed' is assumed but pediatric vs. adult distribution is unclear.","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"warning","value":"Antiviral activity findings are exploratory only (n=5); results should not be used to guide clinical decisions.","value_numeric":null},{"paper_doi":"10.1002/art.70257","tag_type":"warning","value":"Study design is cross-sectional/observational; no control group details or diagnostic cut-off values for IFN score or CXCL10 are reported in the abstract, limiting direct clinical application of thresholds.","value_numeric":null}],"summaries":{"what_studied":"A cohort of 46 patients with suspected type I interferonopathies was evaluated for clinical, immunological, genetic, and molecular profiles; the diagnostic utility of IFN signature (RT-qPCR), serum CXCL10/CXCL9 (ELISA), and antiviral activity (rVSV-GFP assay) were assessed alongside whole-exome sequencing (WES).","key_result":"Molecular diagnosis was confirmed in 37/46 patients (80%); IFN signature was positive in 31/34 evaluable patients (91%), with median IFN score significantly higher than controls (p<0.0001); serum CXCL10 correlated with IFN scores (rs=0.4994, p=0.0026); autoantibodies were detected in 67% of patients; antiviral activity varied by phenotype.","limitations":"Small sample size (n=46) limits generalizability; antiviral activity was assessed in only 5 patients; no longitudinal follow-up data reported to confirm diagnostic thresholds over time.","practice_takeaway":"Consider adding serum CXCL10 measurement alongside the IFN signature in the workup for suspected type I interferonopathies — both showed strong discriminative capacity and CXCL10 is a simpler, widely available assay. Patients with a clear interferon signature but no genetic diagnosis may represent a distinct 'undifferentiated interferonopathy' group worth tracking separately."}},{"doi":"10.1016/s1474-4422(26)00140-7","pmid":"42309087","title":"Spontaneous spinal CSF leaks: a rare variant exome sequencing study and functional analysis","journal_title":"The Lancet Neurology","journal_issn":"1474-4422","published_at":"2026-06-17T00:00:00.000Z","url":"https://doi.org/10.1016/s1474-4422(26)00140-7","source_score":39,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-20T13:24:49.261Z","updated_at":"2026-06-20T13:24:49.261Z","tags":[{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"condition","value":"Connective Tissue Disease","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"condition","value":"Spontaneous Intracranial Hypotension","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"condition","value":"Spontaneous Spinal CSF Leak","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"generic","value":"FBN2 (fibrillin-2)","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"sample_size","value":"n=42","value_numeric":42},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"study_design","value":"Rare Variant Exome Sequencing Study with Functional Validation","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"warning","value":"Patient cohort is 83% women and 90% White, which may limit applicability to male patients and non-White populations.","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"warning","value":"Study design is labeled 'rare variant exome sequencing study with functional validation' — not a standard RCT or cohort study; level of evidence reflects the genetic case-control and in vitro/in vivo nature of the work.","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"warning","value":"The I2394T variant in TB7 accounted for 4 of the 9 FBN2-positive patients (a founder or recurrent variant); this skew may influence the overall enrichment statistics.","value_numeric":null},{"paper_doi":"10.1016/s1474-4422(26)00140-7","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously: authors explicitly recommend integrating FBN2 testing into clinical practice, but the small sample size and lack of prospective validation mean clinical uptake should await further replication.","value_numeric":null}],"summaries":{"what_studied":"Whole-exome sequencing of 42 adults with type 1b spontaneous spinal CSF leaks (Cedars-Sinai, 2006–2019) compared against 3 independent control cohorts (n=3,871 total controls) to identify causative genetic variants, with in vitro fibrillin-2 binding assays and CRISPR-Cas9 mouse models for functional validation.","key_result":"Rare deleterious FBN2 variants were found in 9/42 (21%) patients vs. 5–8% of controls; enrichment was significant across all 3 control cohorts (OR 3.18–5.26, p=0.0003–0.041). Variants clustered in TGF-β binding protein-like (TB) domains and reduced dural fibroblast adhesion in vitro. All 3 Fbn2 mutant mouse lines showed significantly higher CSF leak rates (~73–79%) vs. wild-type (~57%, all p<0.001), while Marfan syndrome mice (Fbn1C1039G/+) showed increased meningeal compliance but no increased leak frequency.","limitations":"- Small patient cohort (n=42), predominantly White women, limiting generalizability to other ethnicities and sexes.\n- Cases were admixed Americans; validation controls were Belgian, raising some population stratification concern despite focus on rare variants.\n- Mouse anatomy differs from humans (thinner dura, quadrupedal posture, no chronic pressure gradient), and the rapid leak-induction protocol cannot replicate decades-long dural compromise seen in patients.","practice_takeaway":"Consider FBN2 genetic testing in patients with type 1b spontaneous spinal CSF leaks, especially those with subtle connective tissue features but no formal syndromic diagnosis. Identifying FBN2 variants may reframe these cases as fibrillinopathies and inform future targeted therapies as they are developed."}},{"doi":"10.1007/s10633-026-10114-w","pmid":"42265353","title":"Oculomotor dysfunction with unremarkable neuroimaging: a diagnostic clue to Gerstmann–Sträussler–Scheinker syndrome","journal_title":"Documenta Ophthalmologica","journal_issn":"0012-4486","published_at":"2026-06-09T00:00:00.000Z","url":"https://doi.org/10.1007/s10633-026-10114-w","source_score":8,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-17T13:29:44.694Z","updated_at":"2026-06-17T13:29:44.694Z","tags":[{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"condition","value":"Gerstmann-Sträussler-Scheinker Syndrome","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"condition","value":"Prion Disease","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"condition","value":"Spinocerebellar Ataxia","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"modality","value":"Video-Oculography","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"sample_size","value":"n=1","value_numeric":1},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"study_design","value":"Case Report","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"warning","value":"Full article text was not accessible — some clinical details (e.g., EEG, CSF results, disease timeline) may exist in the full paper but are not reflected here.","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"warning","value":"Single case report (n=1); findings cannot be generalized to broader GSS population.","value_numeric":null},{"paper_doi":"10.1007/s10633-026-10114-w","tag_type":"warning","value":"The 'older_adult' age tag is applied loosely; the patient is 56 years old, which straddles adult/older_adult categories depending on the classification system used.","value_numeric":null}],"summaries":{"what_studied":"A 56-year-old woman with progressive gait instability, dizziness, and speech difficulties was evaluated with video-oculography (VOG) and whole-exome sequencing (WES) after standard SCA genetic panels (12 subtypes) and neuroimaging were non-diagnostic.","key_result":"VOG revealed spontaneous upbeat nystagmus, macro-square wave jerks, horizontal gaze-evoked nystagmus, saccadic hypermetria, and decreased optokinetic nystagmus. WES identified a heterozygous PRNP p.Pro102Leu (P102L) mutation, confirming GSS — despite unremarkable MRI and negative SCA panel.","limitations":"Single case report limits generalizability. Full-text data (e.g., disease progression, CSF/EEG findings, follow-up duration) were not accessible for review. The oculomotor pattern described may overlap with other cerebellar disorders.","practice_takeaway":"When standard SCA panels and MRI are negative in a patient with progressive ataxia and a family history, detailed video-oculography findings (especially upbeat nystagmus and macro-square wave jerks) should prompt whole-exome sequencing including PRNP. Do not rule out GSS based on normal neuroimaging alone."}},{"doi":"10.1001/jamaneurol.2026.1634","pmid":"42258190","title":"Pathology and Genetics in a Global Cohort of Parkinsonian Disorders","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-06-08T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13247843/","source_score":31,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-17T13:29:42.103Z","updated_at":"2026-06-17T13:29:42.103Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Alzheimer Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Corticobasal Syndrome","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Dementia With Lewy Bodies","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Multiple System Atrophy","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Parkinson Disease","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Parkinson Disease Dementia","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"condition","value":"Progressive Supranuclear Palsy","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"generic","value":"GBA1 variant","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"generic","value":"LRRK2 variant","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"sample_size","value":"n=3353","value_numeric":3353},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"warning","value":"Full text was not accessible; summary is based solely on the abstract and results excerpt. Some detail (e.g., subgroup breakdowns, covariate adjustments) may be missing.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"warning","value":"GBA1 and LRRK2 are tagged as 'generic' drug names as a best fit; they are genetic variants, not drugs — no standard drug tag type exists for genetic markers.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"warning","value":"Level of evidence assigned as 3 (retrospective cross-sectional brain bank study); some may classify brain bank autopsy studies differently depending on framework used.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.1634","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously — the scale and multiancestry nature of the findings are notable, but the retrospective and autopsy-selected design limits direct clinical translation.","value_numeric":null}],"summaries":{"what_studied":"This multicenter, retrospective, autopsy-confirmed brain bank study evaluated clinicopathological correlation, diagnostic accuracy, genetic associations with pathology, and ancestry-related differences in 3,353 donors with parkinsonian disorders (or neurologically normal controls) from 11 academic brain banks in the UK, US, and Australia (enrolled 1985–2024).","key_result":"Misdiagnosis rates ranged from ~10–20% across movement disorders. Dementia with parkinsonism (PDD/DLB) was more strongly linked to Lewy body pathology than PD without dementia (OR 1.96; 95% CI 1.30–3.04). GBA1 carriers had greater Lewy body burden than noncarriers (OR 1.94) and LRRK2 carriers (OR 7.44). AD copathology was present in 40% of Lewy body disease cases. Ancestry-related differences in pathology were significant: South Asian donors were more likely to have PSP pathology; Ashkenazi Jewish donors were more likely to have Lewy body disease (independent of GBA1/LRRK2 status).","limitations":"- Brain bank cohorts have inherent selection bias (donors who consent to autopsy may not represent the broader parkinsonian population).\n- The study is cross-sectional and retrospective, limiting causal inference.\n- Full-text data were not available for detailed review; only abstract and results sections were accessible.","practice_takeaway":"Clinicians should anticipate ~10–20% misdiagnosis rates in parkinsonian disorders and recognize that AD copathology is common in Lewy body disease (40% of cases). Genetic profiling (especially GBA1 status) and patient ancestry should inform diagnostic workup and future trial stratification."}},{"doi":"10.1001/jamaoncol.2026.2091","pmid":"42218736","title":"Impact of Population-Based Pathogenic Variant Testing on Risk-Based Breast Screening Recommendations","journal_title":"JAMA Oncology","journal_issn":"2374-2437","published_at":"2026-05-31T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13224042/","source_score":41,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-10T14:23:44.784Z","updated_at":"2026-06-10T14:23:44.784Z","tags":[{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"condition","value":"Breast Cancer","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"generic","value":"BRCA1/2 and other high/moderate-penetrance breast cancer gene pathogenic variants","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"modality","value":"Breast MRI Screening","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"modality","value":"Mammography","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"modality","value":"Polygenic Risk Score","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"sample_size","value":"n=712","value_numeric":712},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"study_design","value":"Cohort Study","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"warning","value":"CHEK2 is listed as 'low penetrance' in this study's classification — clinicians should note this may differ from other guideline frameworks.","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"warning","value":"Full text was not fully accessible; summary is based on the abstract and results sections only.","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"warning","value":"The specific genes included under 'high-penetrance' and 'moderate-penetrance' categories are not detailed in the available text.","value_numeric":null},{"paper_doi":"10.1001/jamaoncol.2026.2091","tag_type":"warning","value":"The WISDOM trial population may skew toward women who opted into a risk-based screening trial, which could affect generalizability.","value_numeric":null}],"summaries":{"what_studied":"This cohort study used retrospective data from the WISDOM trial (n=712 women aged 40–74 with a pathogenic variant, followed Sep 2016–Sep 2025) to evaluate how often PV carriers would have been correctly identified for high-risk breast screening using a clinical risk model (BCSC) alone or combined with a polygenic risk score (PRS), vs. actual PV-based assignment.","key_result":"PV testing identified high-risk women largely missed by other methods: only 2 of 232 high-penetrance PV carriers (0.9%) would have received the same high-risk screening assignment using clinical + PRS. Among PV carriers aged 40–49, 63.8% (178/279) would have been told to defer screening until age 50; among those aged 50–74, 88.9% (385/433) would have been assigned only biennial mammography.","limitations":"Retrospective cohort design limits causal inference; findings are from a single clinical trial (WISDOM) and may not generalize to all populations; full-text verification was limited by access restrictions.","practice_takeaway":"Clinical risk models and polygenic risk scores alone miss the vast majority of PV carriers who qualify for high-risk MRI-based screening. Population-based PV testing should be integrated into risk-based screening programs to avoid under-screening this high-risk group."}},{"doi":"10.1016/j.jhepr.2026.101902","pmid":"42214790","title":"Genetic testing in liver diseases: Clinical applications","journal_title":"JHEP Reports","journal_issn":"2589-5559","published_at":"2026-05-29T00:00:00.000Z","url":"https://doi.org/10.1016/j.jhepr.2026.101902","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-11T13:26:13.434Z","updated_at":"2026-08-11T13:26:13.434Z","tags":[{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"condition","value":"Acute Liver Failure","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"condition","value":"Cholestatic Liver Disease","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"condition","value":"Cryptogenic Cirrhosis","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"condition","value":"Hepatic Steatosis","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"condition","value":"Idiopathic Portal Hypertension","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"modality","value":"Genomic Sequencing","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"warning","value":"Sex of study population is not applicable given the review design and broad scope.","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"warning","value":"The paper is dated May 2026 but today's date is August 2026, so this is a recently published review; some recommendations may not yet be widely validated in prospective trials.","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.101902","tag_type":"warning","value":"This is a narrative review without original patient data; no sample size is applicable. The impact_flag 'practice_changing' reflects the authors' advocacy for integrating genomic testing into adult hepatology workflows, but supporting primary evidence strength varies by condition and is not quantified in the abstract.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates the clinical applications of genetic testing in adult hepatology, covering a broad spectrum of liver diseases including cholestatic disorders, unexplained hepatic steatosis, cryptogenic cirrhosis, idiopathic portal hypertension, and acute liver failure.","key_result":"Genomic testing is increasingly actionable in adult liver disease; the review synthesises evidence supporting its use in diagnosis and management across multiple hepatic conditions, and advocates for specialised multidisciplinary 'Hepatology Genome Rounds' to optimise clinical translation.","limitations":"As a narrative review, it does not provide original trial data, quantitative outcomes, or meta-analytic pooling; evidence quality and generalisability depend on the underlying primary studies reviewed.","practice_takeaway":"Consider genetic testing early in adults with unexplained hepatic steatosis, cryptogenic cirrhosis, idiopathic portal hypertension, or acute liver failure of unknown cause. Referral to centres with genomic hepatology expertise and multidisciplinary review can improve diagnostic yield and guide management."}},{"doi":"10.1038/s41584-026-01380-8","pmid":"42191839","title":"Decoding variants of uncertain significance in systemic autoinflammatory diseases","journal_title":"Nature Reviews Rheumatology","journal_issn":"1759-4790","published_at":"2026-05-26T00:00:00.000Z","url":"https://doi.org/10.1038/s41584-026-01380-8","source_score":10,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-30T13:22:44.759Z","updated_at":"2026-05-30T13:22:44.759Z","tags":[{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"condition","value":"ADA2 Deficiency","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"condition","value":"Cryopyrin-Associated Periodic Syndrome","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"condition","value":"Familial Mediterranean Fever","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"condition","value":"Systemic Autoinflammatory Diseases","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"modality","value":"Artificial Intelligence / Machine Learning","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"modality","value":"Deep Mutational Scanning","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"modality","value":"Protein Structure Prediction","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"warning","value":"Condition tags for FMF and CAPS are inferred from the genes named (MEFV, NLRP3) in the abstract, not from explicit disease labels in the full text.","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"warning","value":"The paper is classified as a review; no primary sample size is applicable.","value_numeric":null},{"paper_doi":"10.1038/s41584-026-01380-8","tag_type":"warning","value":"The PDF full text was not parseable — all page content was empty. Summary, tags, and takeaways are derived exclusively from the abstract. Specific data, figures, and nuanced arguments from the body of the review could not be captured.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates approaches to classifying variants of uncertain significance (VUS) in systemic autoinflammatory diseases (SAIDs), covering both monogenic and genetically complex disorders, with focus on computational tools (protein structure prediction, ML/AI) and functional assays including multiplexed screens and deep mutational scanning.","key_result":"Large-scale functional studies — including multiplexed assays and deep mutational scanning — have enabled assessment of hundreds of VUS, particularly in *NLRP3*, *MEFV*, and *ADA2*, generating datasets that meaningfully improve variant interpretation and genetic diagnosis.","limitations":"The full text was not extractable from the PDF; summary is based solely on the abstract. Non-coding VUS remain poorly understood, and the predictive accuracy of AI/computational tools must still be validated against functional assays, especially for gain-of-function variants.","practice_takeaway":"When evaluating patients with suspected SAIDs and an inconclusive genetic report, VUS in *NLRP3*, *MEFV*, or *ADA2* may now be further interpreted using emerging deep mutational scanning datasets. Clinicians should not rule out a monogenic autoinflammatory diagnosis based on VUS status alone, and should seek functional data or specialist input before making therapeutic decisions."}},{"doi":"10.1016/j.jaapos.2026.104865","pmid":"42184889","title":"Posterior microphthalmia related to PRSS56 variants in a Saudi cohort: a longitudinal study of visual function","journal_title":"Journal of American Association for Pediatric Ophthalmology and Strabismus","journal_issn":"1091-8531","published_at":"2026-05-25T00:00:00.000Z","url":"https://doi.org/10.1016/j.jaapos.2026.104865","source_score":3,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-30T13:22:43.049Z","updated_at":"2026-05-30T13:22:43.049Z","tags":[{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"condition","value":"Foveoschisis","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"condition","value":"High Hyperopia","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"condition","value":"Posterior Microphthalmia","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"sample_size","value":"n=8","value_numeric":8},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"study_design","value":"Retrospective Longitudinal Case Series","value_numeric":null},{"paper_doi":"10.1016/j.jaapos.2026.104865","tag_type":"warning","value":"Sample size is very small (n=8); findings should be interpreted with caution and not broadly generalized. Two of the 8 patients had only a single visit, so longitudinal conclusions are based on 6 patients. The study population is exclusively from consanguineous Saudi families, which may limit applicability to non-consanguineous or other ethnic populations.","value_numeric":null}],"summaries":{"what_studied":"A retrospective longitudinal case series evaluated clinical, imaging, electrophysiologic, and genetic findings in 8 patients (6 followed 2–16 years, median 10 years) with posterior microphthalmia (PM) due to PRSS56 variants from 4 consanguineous Saudi families, focusing on long-term visual function.","key_result":"All patients had high hyperopia (+12.00 D to +17.75 D), short axial length (12.2–16.4 mm), papillomacular folds, foveoschisis, and ellipsoid zone disruption on OCT. BCVA remained relatively stable over time with limited improvement after age 5; color vision was preserved and visual field depression was mild. Three pathogenic homozygous PRSS56 variants were identified, including a novel nonsense variant c.1405G>T p.(Glu469*).","limitations":"Small sample size (n=8) from a single center limits generalizability. Retrospective design introduces selection bias. Two patients had only a single visit, limiting longitudinal conclusions for those individuals.","practice_takeaway":"In children from consanguineous families presenting with extreme hyperopia and short axial length, early genetic testing for PRSS56 variants can confirm PM and guide counseling. Expect BCVA to plateau after age 5, so management efforts should focus on amblyopia treatment in early childhood."}},{"doi":"10.3390/children13050669","pmid":null,"title":"Hidden Cardiac Channelopathies in Children Presenting with Syncope and Seizure-like Events","journal_title":"Children","journal_issn":"2227-9067","published_at":"2026-05-12T00:00:00.000Z","url":"https://doi.org/10.3390/children13050669","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-05-26T13:35:18.449Z","updated_at":"2026-05-26T13:35:18.449Z","tags":[{"paper_doi":"10.3390/children13050669","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"category","value":"Pediatrics","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"condition","value":"Arrhythmogenic Right Ventricular Dysplasia","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"condition","value":"Brugada Syndrome","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"condition","value":"Catecholaminergic Polymorphic Ventricular Tachycardia","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"condition","value":"Long QT Syndrome","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"condition","value":"Seizure","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"condition","value":"Short QT Syndrome","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"condition","value":"Syncope","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"condition","value":"Vasovagal Syncope","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"modality","value":"Electrocardiography","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"modality","value":"Electrophysiological Study","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"modality","value":"Exercise Testing","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"modality","value":"Holter Monitoring","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"sample_size","value":"n=363","value_numeric":363},{"paper_doi":"10.3390/children13050669","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"study_design","value":"Retrospective Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"warning","value":"Genetic analysis was not performed systematically; the true genetic yield in this cohort may be underestimated.","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"warning","value":"The retrospective design and single-center setting (Turkey) may limit applicability to other populations or healthcare systems.","value_numeric":null},{"paper_doi":"10.3390/children13050669","tag_type":"warning","value":"The study uses two different denominators (cardiology-evaluated n=363 vs. total screened population ~2,195 implied) for prevalence estimates — clinicians should interpret both figures carefully.","value_numeric":null}],"summaries":{"what_studied":"This retrospective cross-sectional study evaluated the prevalence of cardiac channelopathies and inherited arrhythmogenic disorders in 363 pediatric patients (mean age 12.2 ± 4.7 years) presenting with syncope, presyncope, seizures, or seizure-like events at a single Turkish center between January 2015 and April 2019.","key_result":"Cardiac channelopathies or ARVD were found in 18 patients (4.9% of cardiology-evaluated patients; 0.82% of the total screened population), including LQTS (n=8), Brugada syndrome (n=3), short QT syndrome (n=3), CPVT (n=2), ARVD (n=1), and malignant early repolarization (n=1). Exercise-related triggers, ventricular ectopy/VT, and abnormal exercise testing were significantly more common in this group (all p<0.001).","limitations":"Single-center retrospective design limits generalizability. The screened population denominator differs from the cardiology-evaluated cohort, making true prevalence estimates uncertain. Genetic analysis was performed only when clinically indicated, potentially missing subclinical cases.","practice_takeaway":"In children with unexplained syncope or seizure-like events, exercise-related triggers, ventricular ectopy, and ECG abnormalities should prompt urgent evaluation for cardiac channelopathies. A multidisciplinary approach—combining 12-lead ECG, Holter monitoring, exercise testing, and family history review—is key to avoiding misdiagnosis and reducing sudden cardiac death risk."}},{"doi":"10.1001/jamaophthalmol.2026.1183","pmid":"42096227","title":"Association of\n FOXC1\n Duplications With Juvenile Open-Angle Glaucoma","journal_title":"JAMA Ophthalmology","journal_issn":"2168-6165","published_at":"2026-05-07T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13154036/","source_score":58,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-11","doi":"10.1001/jamaophthalmol.2026.1183","days":"7","issn":"2168-6165","rank":"1","field":"Clinical Medicine","score":"58","category":"Ophthalmology","categories":["Ophthalmology"],"_categories":["Ophthalmology"]},"pubmed":{"doi":"10.1001/jamaophthalmol.2026.1183","title":"Association of FOXC1 Duplications With Juvenile Open-Angle Glaucoma.","journal":"JAMA ophthalmology","methods":"","results":"$30","abstract":"$31","keywords":[],"pubmed_id":"42096227","conclusions":"","publication_date":"2026-05-07T00:00:00"},"crossref":{"DOI":"10.1001/jamaophthalmol.2026.1183","URL":"https://doi.org/10.1001/jamaophthalmol.2026.1183","ISSN":["2168-6165"],"link":[{"URL":"https://jamanetwork.com/journals/jamaophthalmology/articlepdf/2848368/jamaophthalmology_maxwell_2026_oi_260020_1776890875.22484.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Association of\n FOXC1\n Duplications With Juvenile Open-Angle Glaucoma"],"author":[{"given":"Giorgina E.","family":"Maxwell","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia, Australia"}]},{"given":"Joshua M.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia, Australia"}]},{"given":"Antonia","family":"Kolovos","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia, Australia"},{"name":"Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia"}]},{"given":"Thi T.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia, Australia"},{"name":"Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia"}]},{"given":"Katherine","family":"Zamora-Alejo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia, Australia"}]},{"given":"Jonathan B.","family":"Ruddle","sequence":"additional","affiliation":[{"name":"Glaucoma Investigation and Research Unit, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia"},{"name":"Ocular Genetics Clinic, The Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia"},{"name":"Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia"}]},{"given":"Michael Alex","family":"Craig","sequence":"additional","affiliation":[{"name":"Karratha Eyecare, Karratha, Western Australia, Australia"}]},{"given":"Mark","family":"Walland","sequence":"additional","affiliation":[{"name":"Glaucoma Investigation and Research Unit, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia"}]},{"given":"Anne M. V.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Glaucoma Investigation and Research Unit, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia"}]},{"given":"Krzysztof","family":"Bernatowicz","sequence":"additional","affiliation":[{"name":"Adult Genetics Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia"}]},{"given":"Carmela B.","family":"Guevarra","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts"}]},{"given":"Francis Raymond","family":"Castor","sequence":"additional","affiliation":[{"name":"Calamba Eye Center-Calamba Medical Center, Laguna, Philippines"}]},{"given":"Edward Ryan","family":"Collantes","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Manila Doctors Hospital, Manila, Philippines"},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts"}]},{"given":"Michael C.","family":"Sibulo","sequence":"additional","affiliation":[{"name":"Eye Institute, St Luke’s Medical Center, Quezon City, Philippines"}]},{"given":"Owen M.","family":"Siggs","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia, Australia"},{"name":"Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia"}]},{"given":"Janey L.","family":"Wiggs","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Manila Doctors Hospital, Manila, Philippines"}]},{"given":"Jamie E.","family":"Craig","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia, Australia"},{"name":"Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia"}]},{"given":"Emmanuelle","family":"Souzeau","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia, Australia"}]}],"issued":{"date-parts":[[2026,5,7]]},"member":"10","prefix":"10.1001","source":"Crossref","volume":null,"created":{"date-time":"2026-05-07T15:30:32Z","timestamp":1778167832000,"date-parts":[[2026,5,7]]},"indexed":{"date-time":"2026-05-07T16:14:20Z","timestamp":1778170460453,"date-parts":[[2026,5,7]]},"subject":[],"abstract":"$32","language":"en","relation":{},"resource":{"primary":{"URL":"https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2848368"}},"subtitle":[],"deposited":{"date-time":"2026-05-07T15:30:36Z","timestamp":1778167836000,"date-parts":[[2026,5,7]]},"issn-type":[{"type":"print","value":"2168-6165"}],"published":{"date-parts":[[2026,5,7]]},"publisher":"American Medical Association 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They accounted for 13.5% (95% CI, 6.7%–25.3%) of JOAG probands with a genetic diagnosis in ANZRAG (second only to *MYOC* at 53.8%), and 9.5% (95% CI, 2.7%–28.9%) in the MEE cohort. Systemic features were mild and uncommon (10.5% of participants).","limitations":"- Small sample (n=20 from 10 families) yields wide confidence intervals, limiting precision of prevalence estimates.\n- Retrospective design with potential ascertainment bias toward more severely affected individuals.\n- Study of a rare condition where individual variants explain only a subset of cases, restricting generalizability.","practice_takeaway":"Consider routine copy-number variant (CNV) analysis in patients with JOAG, as *FOXC1* duplications are an underrecognized but highly penetrant monogenic cause. Unlike classic *FOXC1* deletions, these duplications may present with minimal systemic features, making genetic testing the key diagnostic trigger."}},{"doi":"10.1093/ckj/sfag121","pmid":null,"title":"Ten tips for ordering, interpreting, and communicating genetic test results in nephrology","journal_title":"Clinical Kidney Journal","journal_issn":"2048-8505","published_at":"2026-04-21T00:00:00.000Z","url":"https://doi.org/10.1093/ckj/sfag121","source_score":27,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:50:38.408Z","updated_at":"2026-05-07T22:50:38.408Z","tags":[{"paper_doi":"10.1093/ckj/sfag121","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag121","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag121","tag_type":"condition","value":"Chronic Kidney Disease","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag121","tag_type":"condition","value":"Genetic Kidney Disease","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag121","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag121","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag121","tag_type":"modality","value":"Genetic Testing","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag121","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag121","tag_type":"warning","value":"No original patient data are presented; all recommendations are expert/consensus-based, so level of evidence is inherently limited.","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag121","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the educational scope of the review for many practicing nephrologists, not a trial-based finding.","value_numeric":null},{"paper_doi":"10.1093/ckj/sfag121","tag_type":"warning","value":"The review mentions secondary findings and misattributed parentage as consent considerations — clinicians should be aware these topics require careful local policy and counselling frameworks.","value_numeric":null}],"summaries":{"what_studied":"A practical review offering 10 tips for nephrologists on how to order, interpret, and communicate genetic test results — covering test selection, informed consent, variant classification, and multidisciplinary collaboration in routine nephrology care.","key_result":"The review outlines a structured framework: prioritize early genetic testing when results could change management, use careful phenotyping (including extra-renal features) to guide test choice (single-gene, panel, exome, or genome), treat variants of uncertain significance as hypotheses rather than diagnoses, and schedule periodic reanalysis as classifications evolve.","limitations":"This is a narrative review without original data, systematic methodology, or quantitative outcomes; recommendations reflect expert opinion and may not be generalizable across all healthcare settings or genetic testing infrastructures.","practice_takeaway":"Order genetic testing early when a molecular diagnosis could plausibly change management — don't wait until other workup is exhausted. Treat variants of uncertain significance as hypotheses, not diagnoses, and plan periodic reanalysis as gene–disease evidence evolves."}},{"doi":"10.1038/s41433-025-04216-z","pmid":"41514076","title":"Inherited retinal disorders in Scotland: A 5 year assessment","journal_title":"Eye","journal_issn":"0950-222X","published_at":"2026-01-10T00:00:00.000Z","url":"https://doi.org/10.1038/s41433-025-04216-z","source_score":3,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-01-13","doi":"10.1038/s41433-025-04216-z","days":"7","issn":"0950-222X","rank":"9","field":"Clinical Medicine","score":"3","category":"Ophthalmology","categories":["Ophthalmology"],"_categories":["Ophthalmology"]},"pubmed":{"doi":"10.1038/s41433-025-04216-z","title":"Inherited retinal disorders in Scotland: A 5 year assessment.","journal":"Eye (London, England)","methods":"","results":"532 patients were included in the analysis. The most common clinical diagnosis was retinitis pigmentosa (RP) (42.4%), followed by Stargardt Disease (9.0%), with Usher syndrome the most common syndromic RP. The most common initial test was a 176 gene panel, followed by direct testing for ABCA4, with different regions pursuing different testing strategies. 67.4% of patients received a molecular diagnosis. The most common causal gene was ABCA4, followed by USH2A and RDS/PRPH2.","abstract":"$33","keywords":[],"pubmed_id":"41514076","conclusions":"This study provides the first assessment of IRDs in Scotland over a 5 year period. We demonstrate that the most common clinical diagnoses are RP and Stargardt disease, and that the majority received a molecular diagnosis. This work provides a unique insight into the Scottish ophthalmic genetics service and serves as a benchmark for iterative improvement.","publication_date":"2026-01-10T00:00:00"},"crossref":{"DOI":"10.1038/s41433-025-04216-z","URL":"https://doi.org/10.1038/s41433-025-04216-z","ISSN":["0950-222X","1476-5454"],"link":[{"URL":"https://www.nature.com/articles/s41433-025-04216-z.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s41433-025-04216-z","content-type":"text/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https://www.nature.com/articles/s41433-025-04216-z.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Inherited retinal disorders in Scotland: A 5 year assessment"],"author":[{"given":"James E.","family":"Hazelwood","sequence":"first","affiliation":[]},{"given":"Mertcan","family":"Sevgi","sequence":"additional","affiliation":[]},{"given":"Fiona","family":"Osborne","sequence":"additional","affiliation":[]},{"given":"Blazej","family":"Staniszewski","sequence":"additional","affiliation":[]},{"given":"Nick","family":"George","sequence":"additional","affiliation":[]},{"given":"Andreea","family":"Ionean","sequence":"additional","affiliation":[]},{"given":"David F.","family":"Gilmour","sequence":"additional","affiliation":[]},{"given":"Roly","family":"Megaw","sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2026,1,9]]},"member":"297","prefix":"10.1038","source":"Crossref","volume":null,"created":{"date-time":"2026-01-09T18:03:43Z","timestamp":1767981823000,"date-parts":[[2026,1,9]]},"indexed":{"date-time":"2026-01-10T00:45:55Z","timestamp":1768005955008,"date-parts":[[2026,1,10]]},"license":[{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000,"date-parts":[[2026,1,9]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000,"date-parts":[[2026,1,9]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$34","language":"en","relation":{},"resource":{"primary":{"URL":"https://www.nature.com/articles/s41433-025-04216-z"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"ArticleHistory","label":"Article History"},"label":"Received","order":1,"value":"21 April 2025"},{"name":"revised","group":{"name":"ArticleHistory","label":"Article History"},"label":"Revised","order":2,"value":"2 December 2025"},{"name":"accepted","group":{"name":"ArticleHistory","label":"Article History"},"label":"Accepted","order":3,"value":"22 December 2025"},{"name":"first_online","group":{"name":"ArticleHistory","label":"Article History"},"label":"First Online","order":4,"value":"9 January 2026"},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"},"order":1,"value":"The authors declare no competing of interests."}],"deposited":{"date-time":"2026-01-09T18:03:44Z","timestamp":1767981824000,"date-parts":[[2026,1,9]]},"issn-type":[{"type":"print","value":"0950-222X"},{"type":"electronic","value":"1476-5454"}],"published":{"date-parts":[[2026,1,9]]},"publisher":"Springer Science and Business Media LLC","reference":[{"DOI":"10.1136/bmjopen-2013-004015","key":"4216_CR1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"A comparison of the causes of blindness certifications in England and Wales in working age adults (16–64 years), 1999–2000 with 2009–2010 BMJ Open. https://bmjopen.bmj.com/content/4/2/e004015.short.","article-title":null,"journal-title":null,"doi-asserted-by":"crossref"},{"DOI":"10.1038/s41433-020-0864-6","key":"4216_CR2","year":"2020","issue":null,"author":"F Rahman","volume":"34","first-page":"1271","unstructured":"Rahman F, Zekite A, Bunce C, Jayaram H, Flanagan D. 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