摘要目的:对3例X连锁先天性肾上腺发育不良(X-linked adrenal hypoplasia congenita, XL-AHC)患者进行遗传病因分析，以提高对此病的认识。方法:收集3例XL-AHC患者及家属外周血提取基因组DNA，采用全外显子组测序筛选出致病基因，并进行Sanger测序和家系验证。结果:3例先证者均在幼年诊断为原发性肾上腺皮质功能不全，青春期出现低促性腺激素性性腺功能低下而无青春期发育。基因检测发现先证者1携带NR0B1基因c.420delG(p.R141Gfs*123)半合子突变，其母为c.420delG杂合突变携带者，临床表型正常，其弟弟未携带该突变，符合X连锁隐性遗传。先证者2和先证者3均携带NR0B1基因c.212_213delAA(p.K71Rfs*41)半合子突变。检索人类基因突变数据库未见c.420delG和c.212_213delAA突变报道，提示为新的致病突变。结论:本研究在3例XL-AHC患者中发现2个新的NR0B1基因突变c.420delG及c.212_213delAA，对于发病早的肾上腺皮质功能减退的男性，应警惕XL-AHC可能，及早进行NR0B1基因筛查有助于本病的早期诊断。

abstractsObjective: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.