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Exome sequencing in a three‑generation family with atrial septal defects identified a candidate variant in SRPK2 (HGNC:11306) for congenital heart disease (MONDO_0005453). Specifically, the c.2044C>T (p.Pro682Ser) variant was detected in 2 affected probands (PMID:27989580), and segregation analyses indicated co‑segregation with the disease phenotype. However, previous functional studies did not reveal significant alteration of protein signaling, thereby reducing confidence in the variant’s pathogenic role.
Although the genetic data from this familial case supports a possible contribution of SRPK2 to congenital heart disease, the conflicting functional evidence leaves the association in doubt. Consequently, the overall gene‑disease association is classified as disputed. Additional independent studies are required to resolve these discrepancies and to clarify the clinical utility of incorporating SRPK2 genetic findings into diagnostic decision‑making.
Gene–Disease AssociationDisputedEvidence from a three‑generation family with 2 affected probands (PMID:27989580) showed co‑segregation of the SRPK2 c.2044C>T (p.Pro682Ser) variant with congenital heart disease; however, prior functional studies significantly weaken its candidacy. Genetic EvidenceLimitedThe genetic evidence is restricted to a single family with 2 affected individuals, and the variant has not been recurrently reported in independent cohorts (PMID:27989580). Functional EvidenceLimitedFunctional assays demonstrated minimal impact on protein signaling, which does not support a robust pathogenic mechanism for SRPK2 in congenital heart disease (PMID:27989580). |