title: Mutation screening of the EYA1, SIX1, and SIX5 genes in an East Asian cohort with branchio-oto-renal syndrome.
abstract: OBJECTIVE
  To explore the genetic characteristics of branchio-oto-renal (BOR) syndrome in an East Asian population.
  
  
  METHODS
  Prospective clinical genetic study.
  
  
  METHODS
  Twelve families (total of 18 patients) who fulfilled the criteria for BOR syndrome were enrolled in this study. Mutation screening of the EYA1, SIX1, and SIX5 genes was performed by direct sequencing and quantitative polymerase chain reaction, and genotype-phenotype correlation was investigated.
  
  
  RESULTS
  Two novel EYA1 variants, c.466C>T (p.Q156X) and c.1735delG (p.D579fs), were identified in two multiplex families. The c.466C>T variant resulted in a truncated EYA1 protein, whereas the c.1735delG variant was predicted to encode an EYA1 protein with an abnormal C terminal. Neither variant was identified in a panel of 100 normal controls, and both were cosegregated with the BOR phenotype in the pedigrees, indicating that they were pathogenic mutations. No SIX1 and SIX5 mutations were detected in members of the remaining 10 families. Analysis of the genotype-phenotype correlation revealed a high phenotypic variability between and within BOR families.
  
  
  CONCLUSIONS
  Two novel EYA1 mutations (c.466C>T and c.1735delG) were identified in two families with BOR syndrome. SIX1 and SIX5 mutations were not detected in the present study. Further investigation is warranted regarding the contribution of SIX1 and SIX5 mutations to BOR syndrome in East Asian populations.
authors.affiliation: Department of Otolaryngology, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan.
authors.forename: Shih-Hao
authors.initials: SH
authors.lastname: Wang
authors.forename: Chen-Chi
authors.initials: CC
authors.lastname: Wu
authors.forename: Ying-Chang
authors.initials: YC
authors.lastname: Lu
authors.forename: Yin-Hung
authors.initials: YH
authors.lastname: Lin
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Su
authors.forename: Wuh-Liang
authors.initials: WL
authors.lastname: Hwu
authors.forename: I-Shing
authors.initials: IS
authors.lastname: Yu
authors.forename: Chuan-Jen
authors.initials: CJ
authors.lastname: Hsu
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D019280:Branchio-Oto-Renal Syndrome / Q000208:ethnology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing / Q000379:methods*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D009136:Muscular Dystrophies; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C099236:SIX1 protein, human; C106687:SIX5 protein, human; D004247:DNA; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases