21羟化酶缺陷症14例临床和遗传学分析  

Clinical and genetic analysis of 14 cases with 21 - hydroxylase deficiency

作　　者：王丽红[1] 冯梅[1] 薛晋杰[2] 苏艳花 张改秀[1] 王蕾[1] 陈晓娟[1] 薛慧琴[2] 孟庆明[3] 宋文惠[1] 

机构地区：[1]山西省儿童医院内分泌遗传代谢科,太原030013 [2]山西省儿童医院医学遗传科,太原030013 [3]山西省儿童医院泌尿外科,太原030013

出　　处：《中华实用儿科临床杂志》2017年第20期1563-1567,共5页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的分析21羟化酶缺陷症（21-OHD）的临床表型和基因型的相关性及基因突变频率特点，为临床提供分子层面的诊断依据，并指导早期治疗。方法收集2008年9月至2016年12月在山西省儿童医院内分泌遗传代谢科诊断为21-OHD的14例患儿临床资料、实验室检查，应用下一代高通量测序法（NGS）联合多重连接探针扩增技术（MLPA）对CYP21A2基因进行点突变和大片段缺失/重复检测，对获选的变异位点利用Sanger测序验证，并对其父母进行家系共分离验证。结果14例患儿中失盐型9例，单纯男性化型5例；10例复合杂合突变，4例纯合突变。共发现8种基因突变类型，其中I2G [50%（14/28）]、I173N[21.4%（6/28）]是最常见的2种类型，其次为Arg357Trp[10.7%（3/28）]，而del[10.7%（3/28）]分别为E247fs、Gly111fs、R484fs，另外Q319X[3.6%（1/28）]、Arg355His[3.6%（1/28）]较少见。错义突变10例，剪接位点突变14例，移码突变3例，无义突变1例。突变均来自父母。失盐型最常见的突变为I2G [50%（9/18）]，而单纯男性化型最常见的突变为I173N [50%（5/10）]。临床表型和基因型基本相符。结论通过基因测序，结合临床表型和实验室检查进行全面综合分析疑似病人，有助于早期诊断及鉴别诊断，积极治疗，改善预后，并提供遗传咨询。ObjectiveTo analyze the correlation of clinical phenotype and genotype and gene mutation frequency characteristics of 21-hydroxylase deficiency, and to provide the basis for clinical diagnosis and methods for early intervention.MethodsThe clinical phenotypic signs and examination results of 14 cases with 21-hydroxylase deficiency were collected from September 2008 to December 2016 in Children′s Hospital of Shanxi Province.Point mutations, deletions and conversion mutations for gene CYP21A2 coding 21-hydroxylase were detected through using next generation sequencing（NGS） and multiplex ligation-dependent probe amplification（MLPA）. The captured mutations were further confirmed with Sanger sequencing.Furthermore, the family members underwent the co-segregation validation through the Sanger sequencing or MLPA in those captured mutated sites.ResultsAmong the total 14 cases, 9 cases were identified as the salt wasting, 5 cases the simple virilizing; 10 cases of compound heterozygous mutations, and 4 cases of homozygous mutations.Analysis of the 14 patients revealed 8 different kinds of mutations in CYP21A2 gene.The most frequent mutations of CYP21A2 gene were I2G [50%（14/28）] and I173N [21.4%（6/28）], followed by Arg357Trp[10.7%（3/28）]. Del[10.7%（3/28）] mutations including E247fs, Gly111fs and R484fs.Q319X[3.6%（1/28）] and Arg355His[3.6%（1/28）] were rarely found.Missense mutation was found in 10 cases, splicing mutation in 14 cases, frameshift mutations in 3 cases, nonsense mutations in 1 case.All of the mutations were inherited from their parents, and no new mutation was found.The most common mutations for salt wasting and simple virilizing were respectively I2G[50%（9/18）] and I173N [50%（5/10）]. Collectively, genotypes and phenotypes were matched with each other.ConclusionsThe combination of clinical phenotypes with laboratory examination by gene sequencing and comprehensive analysis, is helpful to early diagnosis, differential diagnosis and optimized treatment, which will improv

关 键 词：先天性肾上腺皮质增生症 21羟化酶 突变 下一代高通量测序 

分 类 号：R725.8[医药卫生—儿科]