title: SIX1 mutation associated with enlargement of the vestibular aqueduct in a patient with branchio-oto syndrome.
abstract: OBJECTIVE
  : The objectives of this study were to identify SIX1 gene mutations in a patient with branchio-oto syndrome (BO) and to clarify the relationship between SIX1 mutation and enlargement of the vestibular aqueduct (EVA).
  
  
  METHODS
  : A genetic study and retrospective chart review for a patient in whom EYA1 mutation had already been excluded was conducted. We studied a Japanese patient who had autosomal-dominant mixed hearing loss, a unilateral ear pit and unilateral EVA, and who was previously diagnosed as having BO. We searched for SIX1 and SLC26A4 mutations using polymerase chain reaction and direct gene sequencing.
  
  
  RESULTS
  : The patient carried a heterozygous A-->G mutation at nucleotide 386 within exon 1 of SIX1 that resulted in substitution of a cysteine for a tyrosine at codon 129 (Y129C) of the gene product. Y129C is a previously identified SIX1 mutation and was not detected in any of our 164 control chromosomes. No SLC26A4 mutations were identified.
  
  
  CONCLUSIONS
  : Y129C mutation in SIX1 may cause EVA as well as BO.
authors.affiliation: Department of Otolaryngology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Ito
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Noguchi
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Yashima
authors.forename: Ken
authors.initials: K
authors.lastname: Kitamura
mesh_terms: D000328:Adult; D001301:Audiometry, Pure-Tone; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D010375:Pedigree; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D014723:Vestibular Aqueduct / Q000000981:diagnostic imaging / Q000503:physiopathology*
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C099236:SIX1 protein, human; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases