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).
This report describes the familial transmission of AHC over several generations and further expands the number of DAX1 mutations reported in the literature.
We proposed the diagnosis of congenital adrenal hypoplasia in this patient and identified a hemizygous mutation (c.999_1000insCTCA, p.Leu335ThrfsX389) in exon 1 of the DAX1 gene.
We hypothesize that the novel (p.Asp372del) DAX1 mutation might be able to cause a disruption of DAX1 function, and is probably involved in the development of AHC and HH in this patient.
A careful analysis of the pedigree of this family lead to the recognition of an X-linked inheritance pattern, with subsequent confirmation in a female heterozygous carrier of a DAX1 missense mutation c.1274G>T, (p.Arg425Ile).The diagnosis of this condition remains challenging in a developing country, since the manifestations of AHC overlap with those of the much more frequently occurring infections; darkening of the skin is difficult to evaluate and there is a lack of access to routine endocrinological testing.
Genetic analysis of NR0B1 in congenital adrenal hypoplasia patients: identification of a rare regulatory variant resulting in congenital adrenal hypoplasia and hypogonadal hypogonadism without testicular carcinoma in situ.
We proposed the diagnosis of adrenal hypoplasia congenita (AHC) in this patient and identified a hemizygous mutation (c.1130delAinsGT, p.E377GfsX12) in exon 1 of the NR0B1 gene.
Array CGH study confirmed the existence of a deletion in Xp21 of the genes responsible for DMD, GKD and the congenital adrenal hypoplasia (gene DAX1 or NROB1 gene: Xp21.3-21.2).
In this study, we investigated the functional defects of DAX-1 caused by mutations identified in 3 unrelated Korean patients with adrenal hypoplasia congenita.
These findings provide insight into the molecular events by which DAX1 mutations influence the hypothalamus-pituitary-gonadal and hypothalamus-pituitary-adrenal axis and lead to AHC and hypogonadotropic hypogonadism.
DAX-1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1) is an atypical member of the nuclear receptor family and acts as a corepressor of a number of nuclear receptors.