Mutation screening of the TPO gene in a cohort of 192 Chinese patients with congenital hypothyroidism.
Mutation screening of the TPO gene in a cohort of 192 Chinese patients with congenital hypothyroidism.
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192 名中国先天性甲状腺功能减退症患者的 TPO 基因突变筛查。
DOI：
10.1136/bmjopen-2015-010719
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发表时间：
2016-05-12
期刊：
影响因子：
2.9
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Fu C;Xie B;Zhang S;Wang J;Luo S;Zheng H;Su J;Hu X;Chen R;Fan X;Luo J;Gu X;Chen S
人类甲状腺过氧化物酶(TPO)基因缺陷被认为是先天性甲状腺功能减退症(CH)的原因之一。本研究的目的是检测广西中国地区慢性丙型肝炎患者的Tpo基因突变谱及患病率，并探讨其与临床表型的关系。收集广西壮族自治区中国等1 92例CH患者的血样，提取外周血白细胞基因组DNA。通过下一代测序(NGS)对包括TPO在内的10个常见CH相关基因的所有外显子及其外显子-内含子边界进行筛选。新的TPO突变的影响是通过在硅胶研究中进行的。对192例CH患者的TPO进行NGS分析，发现2例患者有3种不同的变异(2/192，1%)。对TPO变异患者的其他CH候选基因进行测序发现，患者1为C.2422delT TPO突变纯合子合并双杂合DUOX2致病变异体(p.R683L/p.L1343F)，例2为TPO致病变异体三等位基因(p.R648Q/p.T561M/p.T561M)。本研究发现了一个新的TPO突变c.1682C>；T/p.T561M；以及四个已知突变：TPO中的c.2422delT/p.C808Afs×24和c.1943C>；T/p.R648Q，DUOX2中的c.2048G>；T/p.R683L和c.4027C>；T/p.L1343F。我们的研究表明，在被研究的中国CH患者中，TPO突变的发生率为1%。在单个患者中可以发现一个或多个CH相关基因的两个以上变异，这些变异结合在一起可能会影响个体的表型。发现了一个新的TPO变异c.1682C>；T/p.T561M，从而扩大了该基因的突变谱。
Defects in the human thyroid peroxidase (TPO) gene are reported to be one of the causes of congenital hypothyroidism (CH) due to dyshormonogenesis. The aim of this study was to examine the TPO mutation spectrum and prevalence among patients with CH in the Guangxi Zhuang Autonomous Region of China and to define the relationships between TPO genotypes and clinical phenotypes. Blood samples were collected from 192 patients with CH in the Guangxi Zhuang Autonomous Region, China and genomic DNA was extracted from peripheral blood leucocytes. All exons of the 10 common CH-associated genes including TPO together with their exon-intron boundaries were screened by next-generation sequencing (NGS). The effect of the novel TPO mutation was investigated by ‘in silico’ studies. NGS analysis of TPO in 192 patients with CH revealed 3 different variations in 2 individuals (2/192, 1%). Sequencing other CH candidate genes in the patients with TPO variants revealed that patient 1 was homozygous for c.2422delT TPO mutation combined with double heterozygous DUOX2 pathogenic variants (p.R683L/p.L1343F) and patient 2 was triallelic for TPO pathogenic variants (p.R648Q/p.T561M/p.T561M). The present study identified a novel TPO variation c.1682C>T/p.T561M; and four known mutations: c.2422delT/p.C808Afs×24 and c.1943C>T/p.R648Q in TPO, c.2048G>T/p.R683L and c.4027C>T/p.L1343F in DUOX2. Our study indicated that the prevalence of TPO mutations was 1% among studied Chinese patients with CH. More than two variations in one or more CH-associated genes can be found in a single patient, and may, in combination, affect the phenotype of the individual. A novel TPO variation c.1682C>T/p.T561M was found, thereby expanding the mutational spectrum of the gene.