title: Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic consequences.
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.
authors.affiliation: Molecular Otolaryngology Research Labs, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Eugene H
authors.initials: EH
authors.lastname: Chang
authors.forename: Maithilee
authors.initials: M
authors.lastname: Menezes
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Meyer
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cucci
authors.forename: Virginie S
authors.initials: VS
authors.lastname: Vervoort
authors.forename: Charles E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
mesh_terms: D019280:Branchio-Oto-Renal Syndrome / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009154:Mutation; D009687:Nuclear Proteins; D010641:Phenotype; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017027:Protein Tyrosine Phosphatases; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases