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.
Material and 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.