甲状腺素合成障碍性甲状腺功能减退症五例分子遗传学分析  

Genetic analysis for 5 congenital hypothyroidism patients due to dyshormonogenesis

作　　者：付春云[1] 张淑杰[1] 罗仕玉 王锦[1] 阳奇[1] 谢波波[1] 陈少科[1] 

机构地区：[1]广西壮族自治区妇幼保健院遗传代谢中心实验室,南宁530003

出　　处：《中华儿科杂志》2016年第6期433-436,共4页Chinese Journal of Pediatrics

基　　金：国家自然科学基金（81260126）

摘　　要：目的 分析甲状腺素合成障碍性甲状腺功能减退症分子遗传学基础.方法 对2013年2月至8月经广西壮族自治区新生儿筛查中心疑诊为甲状腺素合成障碍性甲状腺功能减退症患儿5例,提取患儿及父母外周血基因组DNA,采用Sanger测序方法,对DUOX2、TG、TPO及NIS基因所有外显子进行测序.对新变异位点在100名正常人中进行验证.结果 5例中检出3例患儿携带DUOX2基因突变,例1为c.3340delC和p.R683L复合杂合突变;例2为p.K530X纯合突变;例3为p.E879K杂合突变.未找到TG、TPO及NIS基因突变位点.另2例患儿4个基因外显子未检测突变.将新变异位点c.3340delC和p.R683L在100名正常人中进行验证,未发现该2个变异位点存在.3例DUOX2基因突变患儿均表现为暂时性甲状腺功能减退症.结论 基因检测5例甲状腺激素合成障碍性甲状腺功能减退症,发现2个DUOX2新突变位点（c.3340delC和p.R683L）,DUOX2单等位基因和双等位基因突变均表现为暂时性甲状腺功能减退症.Objective To analyze molecular characteristics of 5 congenital hypothyroidism （CH） patients due to dyshormonogenesis.Method We enrolled 5 CH patients due to dyshormonogenesis who were identified in Newborn Screening Center of Guangxi Zhuang Autonomous Region,China.Blood samples were collected from the patients and their parents,and genomic DNA was extracted from peripheral blood leukocytes.All exons of DUOX2,TG,TPO and NIS gene together with their exon-intron boundaries were screened by next-generation sequencing.Specimens from 100 normal controls were tested for these novel variations.Result No TPO,NIS or TG gene mutations were identified.Direct sequencing of the DUOX2 gene revealed that patient 1 had a compound heterozygote for c.3340delC and p.R683L,patient 2 was homozygous for p.K530X and patient 3 was a heterozygote for p.E879K.Both biallelic and monoallelic heterozygous mutations in DUOX2 were associated with transient CH.Novel mutations included c.3340delC and p.R683L,analysis of 100 healthy subjects without thyroid disease did not show the same change.Conclusion Genetic analysis of TPO,NIS,DUOX2 and TG gene in 5 unrelated CH patients with thyroid dyshormonogenesis revealed two novel DUOX2 mutations,both were biallelic and monoallelic heterozygous mutations in DUOX2 associated with transient CH.

关 键 词：甲状腺功能减退症 突变 DUOX2 分子遗传学 

分 类 号：R581.2[医药卫生—内分泌]