ABSTRACT
Objective:To advance the understanding of X-linked adrenal hypoplasia congenita(XL-AHC)through genetic analysis.Methods:Genomic DNA was extracted from peripheral blood of three patients with XL-AHC and their family members as well. Pathogenic genes were screened with whole exome sequencing followed by Sanger sequencing and pedigree verification.Results:All three probands were diagnosed as primary adrenal insufficiency at early age and developed hypogonadotropic hypogonadism in adolescence. The proband 1 was hemizygous for c. 420delG(p.R141Gfs*123)mutation in exon 1 of NR0B1 gene. His mother was a heterozygous mutation carrier while his brother did not carry the mutation, which was consistent with the X-linked recessive inheritance. A hemizygous mutation c. 212_213delAA(p.K71Rfs*41)of NR0B1 gene was detected in both proband 2 and proband 3. These two novel mutations were not reported in HGMD database.Conclusions:In this study, two novel NR0B1 mutations, c. 420delG and c. 212_213delAA were identified in 3 patients with XL-AHC. For men with early onset of adrenocortical hypofunction, XL-AHC should be considered. Early genetic screening of NR0B1 gene is helpful for early diagnosis.