DIAPH2 – Premature Menopause

This summary describes the association between DIAPH2 and premature menopause based on evidence from a single case report and supporting literature reviews. In the reported case, a 10.5‑year‑old girl presented with ovarian dysgenesis and clinical features of primary ovarian insufficiency, including short stature, pterygium, and hirsutism (PMID:26175800). Cytogenetic analysis revealed a balanced translocation involving the X‐chromosome that caused a chromosomal position effect leading to over‑expression of DIAPH2. Although no specific coding variant was identified in this report, the altered expression pattern implicates DIAPH2 in ovarian function. This gene was also flagged as a candidate in a comprehensive review of genetic causes of ovarian insufficiency (PMID:34794894), further supporting its potential role in the pathogenesis of premature menopause.

However, genetic evidence is limited by the absence of multi‑case segregation data and recurrent pathogenic variants directly linking DIAPH2 to premature menopause. Additionally, while functional studies of DIAPH2 have explored its role in actin regulation in the inner ear (PMID:36689403), no experimental work has yet directly elucidated a mechanism by which DIAPH2 dysregulation leads to ovarian insufficiency. Overall, the clinical utility of this association remains preliminary, and further studies are needed to clarify the gene’s role in premature menopause.

References

• Molecular Cytogenetics • 2015 • Short stature and primary ovarian insufficiency possibly due to chromosomal position effect in a balanced X;1 translocation PMID:26175800
• Best practice & research. Clinical endocrinology & metabolism • 2022 • Genetics of ovarian insufficiency and defects of folliculogenesis PMID:34794894
• PloS One • 2023 • In‑depth genetic and molecular characterization of diaphanous related formin 2 (DIAPH2) and its role in the inner ear PMID:36689403

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