Sex Reversal in a 47,XXY Patient due to a Novel Mutation of NR5A1 Gene: A Case Report

Background The clinical manifestations of disorders of sex development (DSD) are heterogeneous and the etiology is complex. In addition to abnormal sex chromosome karyotypes, clinically, DSD are more often caused by mutations in genes related to sex determination and differentiation. Case presentation We report a patient with a 47,XXY DSD caused by a novel nuclear receptor subfamily 5 group A member 1 ( NR5A1 ) mutation, who presented with a left labial mass and a right inguinal mass, a complete female external genital phenotype, blind vagina, and no uterus or ovaries. This patient had extremely low basal anti-müllerian hormone (AMH) and elevated follicle-stimulating hormone (FSH). Testosterone did not rise significantly after human chorionic gonadotropin (hCG) stimulation. Bilateral gonadal pathology showed massive hyalinization. The gonads were dysplastic testes, and Sanger sequencing of the NR5A1 gene showed A deletion of A at base 329, which resulted in the change of amino acid 110 from lysine to arginine and the premature appearance of a stop codon, leading to significant changes in the structure and quality of this translated protein. Finally, the family selected for female rearing sex. Conclusions If the clinical phenotype of sex chromosome disorders of sex development cannot be explained from the sex chromosome karyotype, the genes related to disorders of sex development should be searched from the molecular genetic level. The gender recommendation of DSD patients should be made cautiously based on a comprehensive analysis of clinical conditions.