永久性甲状腺功能减低症患儿相关基因突变的研究

Mutations of TPO,Duox2,DuoxA2 and Pax8 genes in children with suspected permanent hypothyroidism

目的探讨永久性甲状腺功能减低症患儿的基因突变位点与临床表型的关系。方法回顾2013年至2015年在自贡市新生儿疾病筛查中心诊治并随访的2例及既往诊断的8例永久性甲状腺功能减低症患儿的临床资料,并对其中5例患儿的甲状腺过氧化酶(TPO)、双氧化酶2(Duox2)、双氧化酶辅助因子2(DuoxA2)及甲状腺转录因子Pax8基因采用Sanger方法进行测序,了解其基因突变位点的类型及与临床表型的关系。结果在5例永久性甲状腺功能减低症患儿中,2例为DuoxA2基因突变,1例为Duox2基因突变,以上两种基因突变类型的甲状腺形态均正常;另外2例未检出基因突变,但临床表型为甲状腺缺如。结论DuoxA2、Duox2可能为自贡地区永久性甲状腺功能减低症患儿的主要基因突变类型,但临床表现甲状腺缺如症状患儿的基因突变类型未检出,需今后进一步明确。

Objective To study genetic mutations and their clinical features of children with suspected permanent hypothyroidism and to explore relationship between the gene mutation sites and clinical phenotypes.Methods The clinical data of 2 children with permanent hypothyroidism who were diagnozed,treated and followed-up in Neonatal Screening Center of Zigong City from 2013 to 2015 and 8 previously diagnozed children were retrospectively analyzed,and thyroid peroxidase(TPO),double oxidase 2(Duox2),double oxidase auxiliary factor 2(DuoxA2)and thyroid transcription factor Pax8 gene of 5 children were detected by using Sanger sequencing.The type of gene mutations and their relationships with the clinical phenotypes were studied.Results Among these 5 children with permanent hypothyroidism,2 children had the mutation of DuoxA2 gene and 1 child had the mutation of Duox2 gene,but the appearence of the thyriod gland of 3 children was normal.Other 2 children had no gene mutation detected,but their clinical phenotype was absence of the thyroid gland.Conclusion DuoxA2 and Duox2 gene mutations may be the main gene mutation types in children with suspected permanent hypothyroidism in Zigong region,but the gene mutation types of the children with clinical manifestations of thyroid deficiency and absent tyroid gland have not been detected,which should be further clarified in the future.