title: Next-generation sequencing analysis of twelve known causative genes in congenital hypothyroidism.
abstract: BACKGROUND
  Gene variants have been reported to be associated with congenital hypothyroidism (CH), the purpose of this study was to analyze the mutation spectrum and prevalence of 12 known causative genes (TSHR, PAX8, NKX2.1, NKX2.5, FOXE1, DUOX2, TG, TPO, GLIS3, NIS, SLC26A4 and DEHAL1) in CH in China.
  
  
  METHODS
  Peripheral venous blood samples were collected from the patients. Genomic DNA was extracted from peripheral blood leukocytes. All exons and their exon-intron boundary sequences of the 12 known CH associated genes in 66 CH patients were screened by next-generation sequencing (NGS).
  
  
  RESULTS
  NGS analysis of 12 known CH associated genes revealed that 32 patients (32/66, 48.5%) were detected to have at least one potentially functional variant. 21, 9, 1, 1, 1 and 1 patients were found to have potential pathogenic variants in DUOX2, TG, PAX8, SLC26A4, TSHR and TPO genes, respectively. Novel variants included one DUOX2 and one TPO missense variants of unknown significance (VUS).
  
  
  CONCLUSIONS
  Our study expands the mutation spectrum of DUOX2 and TPO genes. 48.5% CH patients had at least one potential pathogenic variant. We found relatively high frequency of DUOX2 (31.8%) and TG (13.6%) mutations in our cohort.
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, 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 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, 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 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, People's Republic of China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, 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 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, People's Republic of China.
authors.forename: Qifei
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, People's Republic of China.
authors.forename: Jingsi
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Genetic Metabolism, Children's Hospital, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, 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 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, 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 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, 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 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, People's Republic of China.
authors.forename: Rongyu
authors.initials: R
authors.lastname: Chen
authors.affiliation: Endocrinology and Genetic Metabolism of Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092,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 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, People's Republic of China. Electronic address: chenshaoke123@163.com.
authors.forename: Shaoke
authors.initials: S
authors.lastname: Chen
mesh_terms: D002648:Child; D002675:Child, Preschool; D003409:Congenital Hypothyroidism / Q000235:genetics*; D004252:DNA Mutational Analysis; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007231:Infant, Newborn; D020641:Polymorphism, Single Nucleotide
keywords: China; Congenital hypothyroidism; Gene mutations; Next-generation sequencing