title: Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1.
abstract: Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder, characterised by the association of branchial, otic and renal anomalies with variable degrees of severity. We have recently identified EYA1 , a human homologue of the Drosophila eyes absent gene, as the gene underlying this syndrome. The products of both genes share a highly conserved 271 amino acid C-terminal region (eyaHR). The eyaHR was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. We report here on the complete genomic structure of EYA1. This gene consists of 16 coding exons and extends over 156 kb. It encodes various alternatively spliced transcripts differing only in their 5' regions. Sequence analysis of the entire EYA1 coding region was performed for 20 unrelated patients affected by BOR syndrome, and six novel mutations were identified. Among these mutations, two are missense mutations, highlighting amino acid residues essential for the function of the EYA1 protein, and one mutation comprises a de novo Alu insertion into an exon. This insertion presumably occurs by retrotransposition, and the mobile Alu element has a poly(A) tail that is unstable throughout generations. To date, 14 mutations have been detected in BOR patients, all of which are different. However, all the mutations are located within or in the immediate vicinity of the eyaHR; the significance of this clustering is discussed.
authors.affiliation: Unit de Génétique des Déficits Sensoriels, CNRS URA 1968, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: S
authors.initials: S
authors.lastname: Abdelhak
authors.forename: V
authors.initials: V
authors.lastname: Kalatzis
authors.forename: R
authors.initials: R
authors.lastname: Heilig
authors.forename: S
authors.initials: S
authors.lastname: Compain
authors.forename: D
authors.initials: D
authors.lastname: Samson
authors.forename: C
authors.initials: C
authors.lastname: Vincent
authors.forename: F
authors.initials: F
authors.lastname: Levi-Acobas
authors.forename: C
authors.initials: C
authors.lastname: Cruaud
authors.forename: M
authors.initials: M
authors.lastname: Le Merrer
authors.forename: M
authors.initials: M
authors.lastname: Mathieu
authors.forename: R
authors.initials: R
authors.lastname: König
authors.forename: J
authors.initials: J
authors.lastname: Vigneron
authors.forename: J
authors.initials: J
authors.lastname: Weissenbach
authors.forename: C
authors.initials: C
authors.lastname: Petit
authors.forename: D
authors.initials: D
authors.lastname: Weil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019280:Branchio-Oto-Renal Syndrome / Q000235:genetics*; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004251:DNA Transposable Elements / Q000235:genetics; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005796:Genes; D006801:Humans; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D017354:Point Mutation
chemical_list: D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D005136:Eye Proteins; C092694:eya protein, Drosophila