Novel compound heterozygous mutations in the desert hedgehog (DHH) gene in cases of siblings with 46,XY disorders of sexual development

BACKGROUND: Disorders of sex development (DSD) are congenital disorders in which the development of the chromosomal, gonadal, or anatomical sex is atypical. Mutations in various genes can impede gonadal development, hormone synthesis, or hormone function and cause DSD. METHODS: Exome sequencing was performed for two siblings with 46,XY DSD. All mutations identified by exome sequencing were confirmed by Sanger sequencing. RESULTS: The 13-month-old younger sibling had a female appearance of the external genital with a clitoris that was assessed as Prader III and scored 2 in the external masculinization score evaluative test. The 16-year-old elder sibling had severe hypospadias. Exome sequencing revealed compound heterozygous mutations in exon 3 of DHH in the siblings with 46,XY DSD. The frameshift mutation (NM_021044.3: c.602delC) was derived from the father and was predicted to be deleterious. The (c.937G > T) substitution mutation was derived from the mother. CONCLUSIONS: Novel compound heterozygous mutations of DHH led to 46,XY DSD in two siblings. This study expands the phenotypic mutation spectra of DHH in patients with 46,XY DSD.