Mutation screening of the EYA1, SIX1, and SIX5 genes in an East Asian cohort with branchio-oto-renal syndrome
Journal
Laryngoscope
Journal Volume
122
Journal Issue
5
Pages
1130-1136
Date Issued
2012
Author(s)
Abstract
Objectives/Hypothesis: To explore the genetic characteristics of branchio-oto-renal (BOR) syndrome in an East Asian population. Study Design: 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. Copyright ? 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
SDGs
Other Subjects
transcription factor; transcription factor Eya1; transcription factor Six1; transcription factor Six5; unclassified drug; adult; aged; article; Asian; branchiootorenal syndrome; carboxy terminal sequence; child; clinical article; cohort analysis; conduction deafness; congenital blood vessel malformation; controlled study; ear disease; external ear malformation; family; gene deletion; gene mutation; gene sequence; genetic code; genetic screening; genetic variability; genotype phenotype correlation; human; human cell; infant; inner ear malformation; kidney malformation; mixed hearing loss; mutational analysis; nucleotide sequence; pedigree; perception deafness; polymerase chain reaction; preauricular pit; preschool child; priority journal; prospective study; quantitative analysis; school child; single nucleotide polymorphism; Taiwan; Adult; Aged; Blotting, Western; Branchio-Oto-Renal Syndrome; Child; Child, Preschool; DNA; Female; Genetic Association Studies; Genetic Testing; Homeodomain Proteins; Humans; Intracellular Signaling Peptides and Proteins; Male; Muscular Dystrophies; Mutation; Nuclear Proteins; Pedigree; Polymerase Chain Reaction; Prospective Studies; Protein Tyrosine Phosphatases; Taiwan
Type
journal article