Branchio-oto-renal syndrome: The mutation spectrum in EYA1 and its phenotypic consequences†‡
Eugene H. Chang
Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa
Search for more papers by this authorMaithilee Menezes
Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa
Search for more papers by this authorNicole C. Meyer
Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa
Search for more papers by this authorRobert A. Cucci
Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa
Search for more papers by this authorVirginie S. Vervoort
Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina
Greenwood Genetic Center, Greenwood, South Carolina
Search for more papers by this authorCharles E. Schwartz
Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina
Greenwood Genetic Center, Greenwood, South Carolina
Search for more papers by this authorCorresponding Author
Richard J.H. Smith
Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa
Sterba Hearing Research Professor and Vice-Chair, Director, Molecular Otolaryngology Research Laboratories, Department of Otolaryngology, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242Search for more papers by this authorEugene H. Chang
Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa
Search for more papers by this authorMaithilee Menezes
Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa
Search for more papers by this authorNicole C. Meyer
Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa
Search for more papers by this authorRobert A. Cucci
Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa
Search for more papers by this authorVirginie S. Vervoort
Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina
Greenwood Genetic Center, Greenwood, South Carolina
Search for more papers by this authorCharles E. Schwartz
Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina
Greenwood Genetic Center, Greenwood, South Carolina
Search for more papers by this authorCorresponding Author
Richard J.H. Smith
Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa
Sterba Hearing Research Professor and Vice-Chair, Director, Molecular Otolaryngology Research Laboratories, Department of Otolaryngology, 200 Hawkins Drive, University of Iowa, Iowa City, IA 52242Search for more papers by this authorCommunicated by Mark H. Paalman
The supplementary material referred to in this article can be viewed at www.interscience.wiley.com/jpages/1059-7794/suppmat
Abstract
EYA1 mutations cause branchio-oto-renal (BOR) syndrome. These mutations include single nucleotide transitions and transversions, small duplications and deletions, and complex genomic rearrangements. The last cannot be detected by coding sequence analysis of EYA1. We sought to refine the clinical diagnosis of BOR syndrome by analyzing phenotypic data from families segregating EYA1 disease-causing mutations. Based on genotype–phenotype analyses, we propose new criteria for the clinical diagnosis of BOR syndrome. We found that in approximately 40% of persons meeting our criteria, EYA1 mutations were identified. Of these mutations, 80% were coding sequence variants identified by SSCP, and 20% were complex genomic rearrangements identified by a semiquantitative PCR-based screen. We conclude that genetic testing of EYA1 should include analysis of the coding sequence and a screen for complex rearrangements. Hum Mutat 23:582–589, 2004. © 2004 Wiley-Liss, Inc.
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