DFFB – Polycystic Ovary Syndrome

In a recent study of inherited polycystic ovary syndrome (PCOS), DFFB (HGNC:2773) was identified as one of 21 genes harboring likely pathogenic variants among affected families (PMID:36284191). The study included a three‐generation family (Family P01) and validation in a total of 9 families, indicating vertical transmission that is consistent with an autosomal dominant mode of inheritance. Although the overall dataset comprised 24 likely pathogenic variants across diverse genes, the DFFB-specific data remain sparse with uncertain segregation details. A representative variant reported for DFFB is c.123A>T (p.Lys41Asn), which aligns with the criteria for a complete coding change (PMID:36284191). The genetic findings suggest a potential link between DFFB and apoptotic dysregulation in PCOS, but the limited number of affected relatives exhibiting segregation underscores the need for caution in interpreting its clinical impact.

Genetic evidence for DFFB is currently classified as limited; while variants of varying classes were detected in a multi‐patient study, detailed analyses specific to DFFB were not pursued. In silico findings hint at a possible role in the apoptotic pathway, yet dedicated functional experiments remain lacking, limiting the strength of functional evidence. Overall, the combined genetic and preliminary experimental data suggest that DFFB may contribute to the molecular etiology of inherited PCOS, although further familial segregation and gene‐targeted functional studies are required. Key take‑home: DFFB represents a promising but as yet under‐validated candidate gene for PCOS, warranting additional investigation to confirm its diagnostic utility.

References

• Journal of human genetics • 2023 • Whole exome and targeted sequencing reveal novel mutations associated with inherited PCOS condition in an Indian cohort. PMID:36284191

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