NR0B1基因新突变致三例X连锁先天性肾上腺发育不良报道  

Three cases of congenital adrenal hypoplasia with hypogonadotropic hypogonadism due to novel NR0B1 mutation

作　　者：袁晶晶[1] 王玉君 杨文君 谢艳红[1] 莫朝晖[1] 金萍[1] Yuan Jingjing;Wang Yujun;Yang Wenjun;Xie Yanhong;Mo Zhaohui;Jin Ping(Department of Endocrinology,Third Xiangya Hospital,Central South University,Changsha 410007,China)

机构地区：[1]中南大学湘雅三医院内分泌科,长沙410007

出　　处：《中华内分泌代谢杂志》2022年第7期589-594,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(81670730);湖南省自然科学基金(2021JJ31007);湖南省卫生健康委员会科研计划课题(202103061081)。

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.21213delAA(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.21213delAA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.21213delAA, 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。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.

关 键 词：NR0B1 DAX1 突变 X连锁先天性肾上腺发育不良 

分 类 号：R586[医药卫生—内分泌]