Background X-linked adrenal hypoplasia congenita (AHC), due to mutations in the nuclear receptor superfamily 0, group B, member 1 (NR0B1)/dosage-sensitive sex reversal, AHC, critical region on the X chromosome, gene 1 (DAX1) gene, usually presents with a salt-wasting adrenal crisis in infancy and hypogonadotropic hypogonadism (HH) in adolescents.
Additionally, accurate reporting of mutations in NR0B1 and the associated phenotype are important to eventually establish a genotype-phenotype correlation that may help anticipate guidance in AHC.
Conclusions Our report provides evidence that defined point mutations in the DAX-1 gene do not necessarily translate into the same clinical manifestations of AHC, even in patients with the same pedigree.
Moreover, the symptomatic treatment observation provided referential evidence in the treatment of X-linkedAHC associated hypogonadism and bilateral inguinal cryptorchidism.
NR0B1 is the causative gene for X-linked adrenal hypoplasia congenita, characterized by adrenal insufficiency, hypogonadotropic hypogonadism, and infertility.
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.
We further detected upregulation of Wnt/β-catenin-VEGF signaling in the fetal Dax1-deficient testis, suggesting abnormal activation of signaling pathways in the absence of DAX1 as one mechanism of AHC-HH.
X-linked adrenal hypoplasia congenita is a rare cause of primary adrenal insufficiency (PAI) in children due to mutations in NR0B1/DAX1 (nuclear receptor subfamily 0, group B, member 1/dosage-sensitive sex reversal-adrenal hypoplasia congenita at the critical region of the X chromosome, gene 1).
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.
This report describes the familial transmission of AHC over several generations and further expands the number of DAX1 mutations reported in the literature.