A novel DAX-1 mutation in two male siblings presenting with precocious puberty and late-onset hypogonadotropic hypogonadism.

Background The DAX-1 gene is associated with X-linked adrenal hypoplasia congenita (AHC). Our objective was to compare the DAX-1 gene sequence of two male siblings exhibiting different clinical manifestations of AHC. Methods Clinical features were analyzed and laboratory data were collected from both siblings. Genomic DNA was extracted from the peripheral blood leukocytes of the siblings and their parents and the DAX-1 gene exons and intron-flanking regions were amplified by the polymerase chain reaction. The DAX-1 gene sequences were compared following sequencing. Results AHC was diagnosed based on a comprehensive review of the clinical presentation and laboratory tests. Gene analysis revealed a nonsense mutation in DAX-1 gene exon 1 (c.192C>G), resulting in a premature termination codon and a truncated 64-amino acid protein product (p.Tyr64X). 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.