title: A novel splice site mutation in EYA4 causes DFNA10 hearing loss.
abstract: Nonsyndromic autosomal dominant sensorineural hearing loss (SNHL) at the DFNA10 locus was described in two families in 2001. Causative mutations that affect the EyaHR domain of the 'Eyes absent 4' (EYA4) protein were identified. We report on the clinical and genetic analyses of an Australian family with nonsyndromic SNHL. Screening of the EYA4 gene showed the novel polypyrimidine tract variation ca. 1,282-12T > A that introduces a new 3' splice acceptor site. This is the first report of a point mutation in EYA4 that is hypothesized to lead to aberrant pre-mRNA splicing and human disease. The DFNA10 family described is only the fourth to be identified. One individual presented with apparently the same phenotype as other affected members of the family. However, genotyping illustrated that he did not share the DFNA10 disease haplotype. Detailed clinical investigation showed differences in the onset and severity of his hearing loss and thus he is presumed to represent a phenocopy, perhaps resulting from long-term exposure to loud noise.
authors.affiliation: Department of Otolaryngology--Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242, USA. michael-hildebrand@uiowa.edu.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Hildebrand
authors.forename: David
authors.initials: D
authors.lastname: Coman
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: R J McKinlay
authors.initials: RJ
authors.lastname: Gardner
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rose
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: Melanie
authors.initials: M
authors.lastname: Bahlo
authors.forename: Hans-Henrik M
authors.initials: HH
authors.lastname: Dahl
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001299:Audiometry; D001483:Base Sequence; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008126:Lod Score; D008297:Male; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D015534:Trans-Activators / Q000235:genetics*
chemical_list: C117736:EYA4 protein, human; D015534:Trans-Activators