New phenotype caused by a NR5A1 heterozygous mutation—— 46, XX disorder of sex development / 中华内分泌代谢杂志

ABSTRACT

Objective To summarize the clinical manifestations of 46, XX ovotesticular disorder of sex development (DSD) caused by a NR5A1 heterozygous mutation. Methods The first case of 46,XX ovotesticular DSD was caused by a NR5A1 heterozygous mutation in China and was reported with a review of 11 similar cases in the literatures since July 2016. Results A 5. 6-year-old child raised as female was born with ambiguous genitalia. The left gonad was palpable in the inguinal region while the right one was located in abdomen. Gonadal histology showed both ovotestis. Vaginoscopy revealed a short, blind-ending vagina. No uterine was detected by laparoscopy. Repeated karyotype results were 46, XX with SRY gene negative. A heterozygous de novo mutation ( p. Arg92Trp) in the accessory DNA-binding region of NR5A1 gene was found in that child. Conclusions We reported for the first time in China a new phenotype caused by a NR5A1 heterozygous mutation-46,XX ovotesticular DSD. According to the review of literatures, such mutation seemed with incomplete penetrance. It could cause both 46, XX DSD and 46, XY DSD with varied manifestations. The possible underlying mechanism might relate to the impairment of the binding between the mutant protein and target DNA which might lead to a decreased inhibition of the male developmental pathway through downregulation of female antitestis genes.