Abstract
Introduction: Primary ovarian insufficiency (POI) due to single-gene variant is classified as a 46,XX difference of sexual development. Variants in the Helicase Family Member 1 (HFM1) gene are associated with POI in females and non-obstructive azoospermia in males. Case Presentation: We described a case of POI with unique genital characteristics, including clitoromegaly, fusion of the labia majora, an opening of the urethral meatus at the perineum, and the absence of the vaginal opening. Hormonal analysis revealed hypergonadotropic hypogonadism. Genetic testing identified two variants in the HFM1 gene: c.1978-2A>C and c.2681-3T>A. A comprehensive analysis of published cases with HFM1 gene variations was conducted to summarize the range of variants and phenotypes associated with HFM1 gene mutations. Conclusion: This study connects HFM1 gene variants to external genital malformations, expanding the spectrum of phenotypes related to HFM1 mutations. Clinicians should consider the possibility of POI in 46,XX female infants with atypical genitalia and perform genetic testing for HFM1 to avoid leaving out the diagnosis.
Journal Section:
Novel Insights from Clinical Practice
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