山东地区甲状腺异位的先天性甲状腺功能减退症患儿TSHR基因突变研究  

A research on TSHR gene mutations of babies with congenital hypothyroidism due to ectopy in Shandong province

作　　者：张文慧[1] 徐龙芳 陈西贵 杨绪庆[4] 于晓霞[5] 王芳[1] 刘世国[5] 阎胜利[1] 

机构地区：[1]青岛大学医学院附属医院内分泌科,山东省266003 [2]菏泽市妇幼保健院新生儿筛查中心 [3]济宁市妇幼保健院新生儿筛查中心 [4]济南市妇幼保健院新生儿筛查中心 [5]青岛大学医学院附属医院遗传室,山东省266003

出　　处：《中华临床医师杂志（电子版）》2013年第22期14-16,共3页Chinese Journal of Clinicians(Electronic Edition)

基　　金：国家自然科学基金(81170812);山东省人口和计划生育委员会科技计划项目[(2013)年第(5)号]

摘　　要：目的对山东地区由甲状腺异位导致的先天性甲状腺功能减退症(CH)患儿TSHR基因第10外显子进行突变筛查,阐明山东地区CH患者TSHR基因突变类型和特点。方法以89例甲状腺异位导致CH的患儿为研究对象,采集外周血提取DNA,PCR扩增第10外显子,采用直接测序的方法对TSHR基因进行突变筛查。结果在89例研究对象第10外显子测序结果中,发现1个错义突变c.1269G>A(p.V424I),1个SNP位点(rs1991517,c.2181G>C,变异频率18.5%)。对小鼠、大鼠、猫、猪、牛、斑马鱼和人的TSHR蛋白进行同源性比较,结果表明第424密码子编码的氨基酸位于TSHR的保守区,该位点的缬氨酸被异亮氨酸取代(p.V424I)。结论山东地区甲状腺异位导致CH的患者中,TSHR基因第10外显子突变率较低。Objective We studied mutations from exon 10 of TSHR gene in patients with congenital hypothyroidism secondary to ectopy, and identified genetic characteristics of TSHR gene mutations, which plays an important role in gene diagnosis and prenatal diagnosis. Methods After collecting blood samples from 89 babies with congenital hypothyroidism, we extracted genomic DNA and detected exon 10 mutations by PCR as well as direct sequencing. Results A missense mutation c.1269 G〉A（p.V424I） and a SNP（rs1991517, c.2181 G〉C） were found according to direct sequencing of 89 subjects. From the NCBI website, we obtained the TSHR family protein-sequence of various species, including Homo sapiens, Mus musculus, Rattus norvegicus, Danio rerio, Felis catus, Sus scrofa and Bos taurus. Using DNAMAN software, we achieved multiple sequence alignment of the TSHR family of different species. We found that codon 424 where the mutation（p.V424I） was identified, was located in highly conserved region of TSHR. Conclusions We report a heterozygous missense mutation and a SNP in TSHR gene in two out of 89 unrelated CH patients, showing that TSHR gene exon10 mutation rate is relatively low, probably not a main cause of congenital hypothyroidism with ectopy in Shandong province.

关 键 词：先天性甲状腺功能减退症 受体 促甲状腺素 突变 异位 

分 类 号：R725.8[医药卫生—儿科]