title: Clinical and molecular genetic analysis of a Chinese family with congenital X-linked adrenal hypoplasia caused by novel mutation 1268delA in the DAX-1 gene.
abstract: Congenital X-linked adrenal hypoplasia (AHC) is a rare disease characterized by primary adrenal insufficiency before adolescence and by hypogonadotropic hypogonadism (HHG) during adolescence. In this paper, we present a Chinese family with AHC. Two brothers, misdiagnosed with adrenal insufficiency of unknown etiology at the age of 9, were correctly diagnosed with AHC when delayed puberty, HHG, and testicular defects were observed. We investigated the clinical features and identified the dosage-sensitive sex reversal AHC critical region of the X chromosome gene 1 (DAX-1) mutation in this kindred. Direct sequencing of the DAX-1 gene revealed that the two siblings have a novel mutation (1268delA) of which their mother is a heterozygous carrier. This mutation causes a frameshift and a premature stop codon at position 436, encoding a truncated protein. It is important to increase knowledge of the mutational spectrum in genes related to this disease, linking phenotype to genotype.
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ye
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Cheng-jiang
authors.initials: CJ
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Feng-qin
authors.initials: FQ
authors.lastname: Dong
authors.affiliation: Department of Neurosurgery, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tong
mesh_terms: D000309:Adrenal Insufficiency / Q000235:genetics*; D000328:Adult; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D000075262:Hypoadrenocorticism, Familial; D008297:Male; D009154:Mutation
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; C539965:NR0B1 protein, human
keywords: Congenital X-linked adrenal hypoplasia; Hypogonadotropic hypogonadism; Primary adrenal insufficiency