SIX1 mutation associated with enlargement of the vestibular aqueduct in a patient with branchio-oto syndrome

Laryngoscope. 2006 May;116(5):796-9. doi: 10.1097/01.mlg.0000209096.40400.96.


Objectives: : 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.

Conclusion: : Y129C mutation in SIX1 may cause EVA as well as BO.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Audiometry, Pure-Tone
  • Branchio-Oto-Renal Syndrome / genetics*
  • Branchio-Oto-Renal Syndrome / physiopathology
  • DNA Mutational Analysis
  • Female
  • Gene Expression Regulation, Developmental
  • Genetic Predisposition to Disease*
  • Homeodomain Proteins / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Mutation*
  • Nuclear Proteins / genetics
  • Pedigree
  • Prognosis
  • Protein Tyrosine Phosphatases / genetics
  • Severity of Illness Index
  • Tomography, X-Ray Computed
  • Vestibular Aqueduct / diagnostic imaging
  • Vestibular Aqueduct / physiopathology*


  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • SIX1 protein, human
  • EYA1 protein, human
  • Protein Tyrosine Phosphatases