Mutation screening of the EYA1, SIX1, and SIX5 genes in an east asian cohort with branchio-oto-renal syndrome
Article first published online: 23 MAR 2012
Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.
Volume 122, Issue 5, pages 1130–1136, May 2012
How to Cite
Wang, S.-H., Wu, C.-C., Lu, Y.-C., Lin, Y.-H., Su, Y.-N., Hwu, W.-L., Yu, I.-S. and Hsu, C.-J. (2012), Mutation screening of the EYA1, SIX1, and SIX5 genes in an east asian cohort with branchio-oto-renal syndrome. The Laryngoscope, 122: 1130–1136. doi: 10.1002/lary.23217
- Issue published online: 18 APR 2012
- Article first published online: 23 MAR 2012
- Manuscript Accepted: 27 DEC 2011
- Manuscript Revised: 2 DEC 2011
- Manuscript Received: 15 JUN 2011
- National Science Council of the Executive Yuan of the Republic of China. Grant Number: NSC-97-2314-B-002-092-MY3
- National Taiwan University Hospital. Grant Number: NTUH-099-001458
- branchio-oto-renal syndrome;
- hearing loss;
- Level of Evidence: 1b
To explore the genetic characteristics of branchio-oto-renal (BOR) syndrome in an East Asian population.
Prospective clinical genetic study.
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.
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.
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.