title: A 4-bp insertion in the eya-homologous region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10.
abstract: BACKGROUND
  Hereditary hearing impairment (HHI) is a heterogeneous class of disorders that shows various patterns of inheritance and involves a multitude of different genes. Mutations in the EYA4 gene are responsible for postlingual, progressive, autosomal dominant hearing loss at the DFNA10 locus. EYA4 is orthologous to the Drosophila gene eya ("eyes absent"), a key regulator of eye formation. EYA4 plays an important role in several developmental processes.
  
  
  METHODS
  Here we report a Hungarian family displaying sensorineural, progressive hearing impairment. The family comprising four generations with 11 affected and 8 unaffected members was subjected to genome-wide linkage analysis and candidate gene sequencing.
  
  
  RESULTS
  By linkage analysis, the chromosomal region 6q22.3 was shown to segregate with the disease. Mutation analysis of the EYA4 gene, which maps to 6q22.3, revealed an insertion of 4 bp (1558insTTTG) in all affected family members. This insertion creates a frameshift and results in a stop codon at position 379. Hence, nearly the complete "eya homologous region" (eyaHR), which is essential for the protein function, would be deleted in the mutant EYA4 protein if the transcription were found to be stable.
  
  
  CONCLUSIONS
  This family is the third one linked to DFNA10 and revealing a mutation in the EYA4 gene. In all three families, the mutations are localized in different regions of the eyaHR, suggesting that this protein contains several functional subregions with different tissue-specific importance.
authors.affiliation: Department of Otolaryngology, University of Tübingen, Tübingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Pfister
authors.forename: Tímea
authors.initials: T
authors.lastname: Tóth
authors.forename: Holger
authors.initials: H
authors.lastname: Thiele
authors.forename: Birgit
authors.initials: B
authors.lastname: Haack
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Blin
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Zenner
authors.forename: István
authors.initials: I
authors.lastname: Sziklai
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Susan
authors.initials: S
authors.lastname: Kupka
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D006814:Hungary; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics*; D010375:Pedigree; D017385:Sequence Homology; D015534:Trans-Activators / Q000235:genetics*
chemical_list: C117736:EYA4 protein, human; D015534:Trans-Activators