DACH2 – Premature Menopause

The available evidence suggests a limited association between DACH2 and premature menopause. In a mutation analysis study of over 200 Italian patients with premature ovarian failure (PMID:15459172), rare variants in DACH2 were identified, although no single recurrent mutation or robust segregation data was provided. A separate screening in a Hungarian cohort of 48 unrelated patients with premature ovarian insufficiency (PMID:38649916) further assessed a panel of POI‑associated genes including DACH2; however, the data did not yield extensive familial segregation evidence. As such, the clinical validity remains limited due to the lack of multiple unrelated probands with strong segregation or a convergent variant spectrum.

Functional studies provide moderate experimental support for a role of DACH2 in ovarian function. Mouse model investigations demonstrated that deletion of Dach2 exon 1 abrogates RNA expression without gross developmental defects in the eye or brain (PMID:16470613), suggesting that while Dach2 may contribute to subtle reproductive phenotypes, the functional perturbation observed does not fully recapitulate human premature menopause. Taken together, the genetic and functional evidence indicate that DACH2 is a potential contributor to premature menopause, but additional robust data are required to strengthen its clinical utility in diagnostic decision‑making.

References

• Human Reproduction (Oxford, England) • 2004 • Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B PMID:15459172
• Unknown • N/A • Genetic analysis of premature ovarian insufficiency in a Hungarian cohort PMID:38649916
• Genesis • 2006 • Mouse Dach2 mutants do not exhibit gross defects in eye development or brain function PMID:16470613

Evidence Based Scoring (AI generated)