Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism

• Published in: Journal of pediatric endocrinology & metabolism : JPEM Vol. 28; no. 7-8; p. 809
• Main Authors: Qin, Guijun, Ji, Hongfei, Li, Xialian, Ma, Xiaokun, Wang, Danping
• Format: Journal Article
• Language: English
• Published: Germany 01-07-2015
• Subjects: Adolescent; Adrenal Insufficiency - genetics; Adrenal Insufficiency - pathology; Adult; Child; Child, Preschool; China; DAX-1 Orphan Nuclear Receptor - genetics; DNA Mutational Analysis; Female; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - pathology; Humans; Hypoadrenocorticism, Familial; Hypogonadism - genetics; Hypogonadism - pathology; Male; Mutation - genetics; Pedigree; Polymerase Chain Reaction; Prognosis; China
• ISSN: 2191-0251
• DOI: 10.1515/jpem-2014-0156

To analyze the DAX1 (NR0B1) (dosage-sensitive sex reversal-adrenal hypoplasia congenita (AHC) critical region on the X chromosome gene 1) gene in two Chinese families with AHC and hypogonadotrophic hypogonadism (HHG).
Two families with 4 affected males, 5 carrier females, and 4 unaffected males were investigated. Sequencing of the entire 1413-bp coding region of DAX1 (NR0B1) gene was performed in both patients and their family members.
Two different novel DAX1 (NR0B1) mutations located within exon 1, an insertional mutation at codon 35 leading to a frameshift and a premature stop at codon 46, and a deletion mutation at codon 331 leading to a frameshift and a premature stop at codon 371 were detected. The mothers and sisters of the patients were heterozygotes for the mutations, while their fathers did not carry the mutations.
Two novel DAX1 (NR0B1) mutations were detected in two Chinese families. These data indicate that molecular analysis of the DAX1 (NR0B1) gene is important for the diagnosis and genetic counseling of children with primary adrenal insufficiency.