title: Mutation screening of the TPO gene in a cohort of 192 Chinese patients with congenital hypothyroidism.
abstract: 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.
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Chunyun
authors.initials: C
authors.lastname: Fu
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Bobo
authors.initials: B
authors.lastname: Xie
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Shujie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Jiasun
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Xuyun
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Rongyu
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Jingsi
authors.initials: J
authors.lastname: Luo
authors.affiliation: Endocrinology and Genetic Metabolism of Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xuefan
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China Guangxi Center for Birth Defects Research and Prevention, Nanning, People's Republic of China.
authors.forename: Shaoke
authors.initials: S
authors.lastname: Chen
mesh_terms: D001324:Autoantigens / Q000235:genetics*; D002675:Child, Preschool; D002681:China; D003198:Computer Simulation; D003409:Congenital Hypothyroidism / Q000235:genetics*; D004252:DNA Mutational Analysis; D000074623:Dual Oxidases / Q000235:genetics; D005091:Exons; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007453:Iodide Peroxidase / Q000235:genetics*; D033862:Iron-Binding Proteins / Q000235:genetics*; D008297:Male; D010641:Phenotype
chemical_list: D001324:Autoantigens; D033862:Iron-Binding Proteins; D000074623:Dual Oxidases; C056658:TPO protein, human; D007453:Iodide Peroxidase; C431515:DUOX2 protein, human
keywords: China; Congenital hypothyroidism; TPO; gene mutations; next-generation sequencing