• PMID: 18202527
• Gene Name: DAX1
• Condition: X-linked adrenalhypoplasia congenita (AHC), hypogonadotropic hypogonadism (HHG)
• Association: Molecular analysis demonstrated two novel point mutations (V269D and L278R) in two patients
• Mutation: V269D, L271X, L278R, and Q395X
• Population size: 4
• Population details: 4 patients with AHC and HHG caused by the mutations of the DAX-1 gene
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: X-linked adrenalhypoplasia congenita (AHC), hypogonadotropic hypogonadism (HHG)

Four Japanese patients with adrenal hypoplasia congenita and hypogonadotropic hypogonadism caused by DAX-1 gene mutations: mutant DAX-1 failed to repress steroidogenic acute regulatory protein (StAR) and luteinizing hormone beta-subunit gene promoter activity

Okuhara K, Abe S, Kondo T, Fujita K, Koda N, Mochizuki H, Fujieda K, Tajima T.

Mutations of DSS (dosage sensitive sex reversal)-AHC critical region on the X chromosome, gene 1 DAX-1(NROB1)] results in X-linked adrenal hypoplasia congenita (AHC) and hypogonadotropic hypogonadism (HHG). Here we report four Japanese patients with AHC and HHG caused by the mutations of the DAX-1 gene. All patients manifested adrenal crisis at early childhood. Three patients did not show any pubertal sign and were diagnosed as having HHG. One patient manifested spontaneous pubertal development at 17 years of age. Nevertheless, his puberty did not develop further and his gonadotropin and testosterone levels decreased thereafter. Therefore, he was also diagnosed as having HHG. We performed testicular biopsy in another patient with HHG. Histological examination demonstrated Sertoli cell hypoplasia and no sperm formation in the seminiferous tubules. Molecular analysis demonstrated two novel point mutations (V269D and L278R) in two patients. Transient transfection assays showed that all these mutations (V269D, L271X, L278R, and Q395X) abolished the repression activity to both StAR and LHbeta gene promoter activation. In conclusion, we reported patients with AHC and HHG caused by the loss of function mutations of the DAX-1 gene. FAU - Okuhara, Koji AU - Okuhara K AD - Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan. FAU - Abe, Shuji AU - Abe S FAU - Kondo, Takuma AU - Kondo T FAU - Fujita, Keinosuke AU - Fujita K FAU - Koda, Noya AU - Koda N FAU - Mochizuki, Hiroshi AU - Mochizuki H FAU - Fujieda, Kenji AU - Fujieda K