title: Mutation screening of the SLC26A4 gene in a cohort of 192 Chinese patients with congenital hypothyroidism.
abstract: OBJECTIVE
  Pendred syndrome (PS) is an autosomal recessive disorder characterised by sensorineural hearing loss and thyroid dyshormonogenesis. It is caused by biallelic mutations in the SLC26A4 gene encoding for pendrin. Hypothyroidism in PS can be present from birth and therefore diagnosed by neonatal screening. The aim of this study was to examine the SLC26A4 mutation spectrum and prevalence among congenital hypothyroidism (CH) patients in the Guangxi Zhuang Autonomous Region of China and to establish how frequently PS causes hearing impairment in our patients with CH.
  
  
  METHODS
  Blood samples were collected from 192 CH patients in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes. All exons of the SLC26A4 gene together with their exon-intron boundaries were screened by next-generation sequencing. Patients with SLC26A4 mutations underwent a complete audiological evaluation including otoscopic examination, audiometry and morphological evaluation of the inner ear.
  
  
  RESULTS
  Next generation sequencing analysis of SLC26A4 in 192 CH patients revealed five different heterozygous variations in eight individuals (8/192, 4%). The prevalence of SLC26A4 mutations was 4% among studied Chinese CH. Three of the eight were diagnosed as enlargement of the vestibular aqueduct (EVA), no PS were found in our 192 CH patients. The mutations included one novel missense variant p.P469S, as well as four known missense variants, namely p.V233L, p.M147I, p.V609G and p.D661E. Of the eight patients identified with SLC26A4 variations in our study, seven patients showed normal size/location of thyroid gland, and one patients showed a decreased size one.
  
  
  CONCLUSIONS
  The prevalence of SLC26A4 pathogenic variants was 4% among studied Chinese patients with CH. Our study expanded the SLC26A4 mutation spectrum, provided the best estimation of SLC26A4 mutation rate for Chinese CH patients and indicated the rarity of PS as a cause of CH.
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.
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.
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.
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.
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, 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.
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.
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.
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.
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.
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, 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, 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.|Boston Children's Hospital, Harvard Medical School, Boston, MA, United States.
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, People's Republic of China.
authors.forename: Shaoke
authors.initials: S
authors.lastname: Chen
mesh_terms: D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006044:Goiter, Nodular / Q000453:epidemiology / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D015997:Neonatal Screening / Q000379:methods; D015995:Prevalence; D000076988:Sulfate Transporters; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014723:Vestibular Aqueduct / Q000002:abnormalities
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D013972:Thyrotropin; D013974:Thyroxine