title: Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR.
abstract: Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by the association of branchial and external ear malformations, hearing loss, and renal anomalies. The phenotype varies from ear pits to profound hearing loss, branchial fistulae, and kidney agenesis. The most common gene mutated in BOR families is EYA1, a transcriptional activator. Over 80 different disease-causing mutations have been published (www.healthcare.uiowa.edu/labs/pendredandbor/, last accessed 20 November 2007). We analyzed the EYA1 coding region (16 exons) from 435 families (345 at the University of Iowa [UI] and 95 at Boys Town National Research Hospital [BTNRH], including five at both) and found 70 different EYA1 mutations in 89 families. Most of the mutations (56/70) were private. EYA1 mutations were found in 31% of families (76/248) fitting established clinical criteria for BOR and 7% of families with questionable BOR phenotype (13/187). Severity of the phenotype did not correlate with type of mutation nor with the domain involved. These results add considerably to the spectrum of EYA1 mutations associated with BOR and indicate that the BOR phenotype is an indication for molecular studies to diagnose EYA1-associated BOR.
authors.affiliation: Department of Genetics, Boys Town National Research Hospital, Omaha, Nebraska 68164, USA.
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Orten
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Fischer
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Sorensen
authors.forename: Uppala
authors.initials: U
authors.lastname: Radhakrishna
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
authors.forename: Henri A M
authors.initials: HA
authors.lastname: Marres
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
authors.forename: Katherine O
authors.initials: KO
authors.lastname: Welch
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: William J
authors.initials: WJ
authors.lastname: Kimberling
mesh_terms: D000595:Amino Acid Sequence; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C104381:EYA1 protein, human; D017027:Protein Tyrosine Phosphatases