This retrospective study applied structural variation sequencing (SVseq) — using mate-pair library construction and high-throughput sequencing — to 26 amniotic fluid samples with partial gene duplications (PGDups) initially detected by chromosomal microarray or sequencing, followed by postnatal phenotypic follow-up of the fetuses.
SVseq resolved PGDup structure in all 26 cases: 22 (84.6%) were tandem duplications (13 extragenic classified as benign/VUS; 9 intragenic classified as P/LP or VUS), 3 (11.5%) were chromosomal complex rearrangements, and 1 (3.8%) had no true duplication. Only 2 of the 9 intragenic tandem duplication cases had obvious postnatal abnormal phenotypes.
Small retrospective cohort (n=26) limits generalizability. Postnatal follow-up duration and completeness are not specified, which may underestimate phenotypic expression. No prospective or comparative arm against a standard-of-care method is included.
When chromosomal microarray or sequencing flags a partial gene duplication prenatally, SVseq can clarify whether the duplication is intragenic (higher pathogenicity risk) or extragenic (likely benign/VUS), enabling more confident counseling. Consider integrating SVseq into prenatal diagnostic workflows for unresolved PGDups, particularly when ultrasound is normal and pathogenicity is uncertain.
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