title: PAX8 pathogenic variants in Chinese patients with congenital hypothyroidism.
abstract: BACKGROUND
  The clinical presentation of patients with congenital hypothyroidism (CH) caused by paired box gene 8 (PAX8) pathogenic variants is variable and PAX8 mutation rates differ significantly among different populations. This study was set to examine the PAX8 mutation spectrum and prevalence among patients with CH in Guangxi Zhuang Autonomous Region, China.
  
  
  METHODS
  Peripheral venous blood samples were collected from the patients. Genomic DNA was extracted from peripheral blood leukocytes. All exons of the 11 known CH associated genes including PAX8 together with their exon-intron boundaries were screened by next-generation sequencing (NGS). Permanent or transient CH was determined using the results of thyroid function tests after temporary withdrawal of L-thyroxine (L-T4) therapy at approximately 2 years of age.
  
  
  RESULTS
  Next generation sequencing analysis of PAX8 in 378 CH patients revealed five different mutations in nine individuals (two are siblings). The mutations included two known missense variants, namely c.92G>A (p.R31H) and c.91C>T (p.R31C), and one novel missense variant c.68G>T (p.G23V), as well as two novel nonsense variants c.1090C>T (p. R364X) and c.658C>T (p.R220X). The variant c.92G>A (p.R31H) is highly recurrent in our patient cohort but the clinical phenotypes vary greatly among those carrying this variant. PAX8 pathogenic variants were mainly associated with permanent CH.
  
  
  CONCLUSIONS
  The prevalence of PAX8 pathogenic variants was 2.38% among patients with CH in Guangxi. Our study expanded the PAX8 mutation spectrum and provided the best estimation of PAX8 mutation rate among CH patients in Guangxi, China.
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: 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 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: 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: 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 530003, People's Republic of China; GuangXi Center for Birth Defects Research and Prevention, Nanning 530003, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
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: 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 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: 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: 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: 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: Shang
authors.initials: S
authors.lastname: Yi
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: Yunli
authors.initials: Y
authors.lastname: Lai
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: 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 530003, People's Republic of China; Boston Children's Hospital, Harvard Medical School, Boston 02115, MA, United States.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Endocrinology and Genetic Metabolism of Institute for Pediatric Research, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Electronic address: gu_xuefan@163.com.
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: D000293:Adolescent; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China; D003409:Congenital Hypothyroidism / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*
chemical_list: D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors
keywords: Chinese patients; Congenital hypothyroidism; Next-generation sequencing; Paired box gene 8