先天性甲状腺功能减退症壮族患儿TSHR基因突变遗传分析

Genetic analysis of TSHR gene mutation in children of Chinese Zhuang nationality with congenital hypothyroidism

目的分析南宁市先天性甲状腺功能减退症壮族患儿促甲状腺激素受体(TSHR)基因突变及其特点。方法以21例患有先天性甲状腺功能减退症的壮族患儿及其父母为研究对象。提取患儿及其父母的外周血DNA,采用荧光定量PCR扩增TSHR基因所有12个外显子、外显子-内含子交界区以及3′端和5′端非翻译区,利用第一代测序法对基因扩增产物进行测序并进行分析。结果21例患儿中的12例存在TSHR基因突变,分别为c.C805A(p.R269S)纯合突变6例,c.C154A(p.P52T)和c.C805A(p.R269S)复合杂合突变1例,c.C805A(p.R269S)杂合子复合c.G2181C(p.E727D)纯合突变1例,c.C805A(p.R269S)杂合子突变4例。40例父母中存在的TSHR位点基因突变分别为c.C154A(p.P52T)1例,c.G2181C(p.E727D)9例,c.C805A(p.R269S)24例。结论先天性甲状腺功能减退症患儿的发病与父母TSHR基因具有遗传相关性,新发现的c.C805A(p.R269S)基因突变位点可能是壮族人群遗传性先天性甲状腺功能减退症的主要突变位点。

Objective To explore the mutation of TSHR gene in the children of Zhuang nationality with congenital hypothyroidism in Nanning city of China and their status.Methods Twenty-one children with congenital hypothyroidism and their parents of Zhuang nationality in Nanning were selected as the research objects in this study.After informed consent,DNA in peripheral blood were extracted from the children and their parents.All the 12 exons of TSHR gene,the exon-intron junction region and the untranslated regions in 3′and 5′ends were amplified by PCR.The amplification products of the gene were sequenced with the first generation sequencing.Results Twelve out of the 21 children were found to display mutations in TSHR gene.Among them,6 cases were C805A(p.R269S)homozygous mutation,1 case was c.C154A(p.P52T)and c.C805A(p.R269S)compound heterozygous mutation,1 case was c.C805A(p.R269S)heterozygous compound c.G2181C(p.E727D)homozygous mutation,4 case was c.C805A(p.R269S)heterozygous mutation.Three TSHR gene mutations were found in the 40 parents,including 1 case of c.C154A(p.P52T),9 cases of c.G2181C(p.E727D),and 24 cases of c.C805A(p.R269S).Conclusion The incidence of Children with congenital hypothyroidism presented genetic correlation with their parental TSHR gene,and the newly discovered TSHR gene mutation site c.C805A(p.R269S)may be the mutation site that causes congenital hypothyroidism in Chinese Zhuang population.