PDF(Pubmed)
Abstract：
Nuclear receptor subfamily 0 group B member 1 gene (NR0B1) encodes an orphan nuclear receptor that plays a critical role in the development and regulation of the adrenal gland and hypothalamic-pituitary-gonadal axis. In this study, we report a novel mutation in NR0B1 that led to adult-onset adrenal hypoplasia congenita (AHC) and pubertal development failure in a male adult. Clinical examinations revealed hyponatremia, elevated adrenocorticotropic hormone levels, reduced testosterone and gonadotropin levels, and hyper-responses to gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests. Whole-exome sequencing and Sanger sequencing were performed to identify the potential causes of AHC. Candidate variants were shortlisted based on the X-linked recessive models. Sequence analyses identified a novel hemizygous variant of c.1034delC in exon 1 of NR0B1 at Xp21.2, resulting in a frameshift mutation and premature stop codon formation. The c.1034delC/p.Pro345Argfs*27 in the NR0B1 gene was detected in the hemizygous state in affected males and in the heterozygous state in healthy female family carriers. These results expand the clinical features of AHC as well as the mutation profile of the causative gene NR0B1. Further studies are needed to elucidate the biological effects of the mutation on the development and function of the adrenal gland and the hypothalamic-pituitary-gonadal axis.
摘要：
核受体亚家族0组B成员1基因（NR0B1）编码孤儿核受体，在肾上腺和下丘脑-垂体-性腺轴的发育和调节中起关键作用。在这项研究中,我们报道了NR0B1中的一个新突变,该突变导致成年男性先天性肾上腺发育不全(AHC)和青春期发育障碍.临床检查显示低钠血症,促肾上腺皮质激素水平升高，睾酮和促性腺激素水平降低，以及对促性腺激素释放激素和人绒毛膜促性腺激素刺激试验的过度反应。进行全外显子组测序和Sanger测序以鉴定AHC的潜在原因。候选变体根据X连锁隐性模型入围。序列分析在NR0B1的Xp21.2外显子1中鉴定了c.1034delC的新型半合子变体，导致移码突变和过早的终止密码子形成。c.1034delC/p。NR0B1基因中的Pro345Argfs*27在受影响的男性中检测到半合子状态，在健康的女性家庭携带者中检测到杂合状态。这些结果扩展了AHC的临床特征以及致病基因NR0B1的突变谱。需要进一步的研究来阐明突变对肾上腺和下丘脑-垂体-性腺轴发育和功能的生物学作用。
