SIX1 mutation associated with enlargement of the vestibular aqueduct in a patient with branchio-oto syndrome.
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.
Ito
Taku
T
Department of Otolaryngology, Tokyo Medical and Dental University, Tokyo, Japan.
Noguchi
Yoshihiro
Y
Yashima
Takatoshi
T
Kitamura
Ken
K
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*
D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C099236:SIX1 protein, human; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases