SRPK2 – Atrial Septal Defect

A recent familial study in congenital heart disease identified a candidate variant in SRPK2 for atrial septal defect (MONDO_0006664). Exome sequencing performed on a three‑generation family, in which two affected individuals harboured the variant, revealed the SRPK2 change c.2044C>T (p.Pro682Ser). Although segregation analysis showed co‑segregation in the affected members (PMID:27989580), the overall genetic support is limited. Competing evidence from a more strongly implicated gene (NOTCH1) and lack of robust functional perturbation in SRPK2 weaken the sole association with atrial septal defect. The modest segregation evidence and the challenge in reconciling functional data with pathogenicity preclude a definitive clinical assertion at this time.

Functional assays failed to demonstrate significant disruption of SRPK2 activity in the context of atrial septal defect, and the variant’s limited recurrence further constrains its diagnostic utility. While SRPK2 is involved in relevant biological pathways that implicate cardiac development, current evidence is insufficient to support its stand‑alone use in clinical diagnostics. Additional functional studies and identification of more affected probands are necessary to clarify its role. In summary, the association of SRPK2 with atrial septal defect is intriguing yet limited, underscoring a need for further investigations before it can be integrated into routine clinical decision‑making.

References

• International journal of cardiology • 2017 • The promises and challenges of exome sequencing in familial, non‑syndromic congenital heart disease PMID:27989580

Evidence Based Scoring (AI generated)