From Primary Amenorrhea to the Desert Hedgehog Gene: Novel Homozygous Variant in 46,XY Gonadal Dysgenesis

Deligözoğlu D., CEYLANER S., GÜRBÜZ F.

Journal of Pediatric and Adolescent Gynecology, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1016/j.jpag.2026.02.006
  • Dergi Adı: Journal of Pediatric and Adolescent Gynecology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
  • Anahtar Kelimeler: Amenorrhea, Desert hedgehog (DHH) gene, DSD, Gonadal dysgenesis
  • Lokman Hekim Üniversitesi Adresli: Evet

Özet

AbstractIntroduction46,XY gonadal dysgenesis is a rare difference of sex development in which individuals have female external genitalia despite a 46,XY karyotype. Pathogenic variants in genes involved in testis determination and differentiation may underlie the condition and should be considered in the evaluation of primary amenorrhea.CaseA 14-year-old girl presented with primary amenorrhea. Hormonal evaluation revealed hypergonadotropic hypogonadism, and imaging demonstrated absence of the uterus and ovaries. Gonadectomy specimens demonstrated testicular tissue. Genetic analysis identified a novel homozygous missense likely pathogenic variant in the Desert Hedgehog (DHH) gene (NM_021044.4:c.983T>C; p.Leu328Pro).ConclusionThe DHH gene plays a critical role in testis differentiation, and pathogenic variants may result in 46,XY gonadal dysgenesis. Hormone replacement therapy and long-term multidisciplinary follow-up are essential components of management.