A 4bp-insertion in the eya-Homologous Region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10

Markus Pfister, Tímea Tóth, Holger Thiele, Birgit Haack, Nikolaus Blin, Hans Peter Zenner, I. Sziklai, Peter Nürnberg, Susan Kupka

Research output: Contribution to journalArticle

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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. 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.

Original languageEnglish
Pages (from-to)607-611
Number of pages5
JournalMolecular Medicine
Volume8
Issue number10
Publication statusPublished - Oct 1 2002

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Hearing Loss
Mutation
Genes
Inheritance Patterns
Terminator Codon
Genetic Association Studies
Mutant Proteins
Drosophila
Proteins
Autosomal Dominant 10 Deafness
Genome

ASJC Scopus subject areas

  • Genetics

Cite this

Pfister, M., Tóth, T., Thiele, H., Haack, B., Blin, N., Zenner, H. P., ... Kupka, S. (2002). A 4bp-insertion in the eya-Homologous Region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10. Molecular Medicine, 8(10), 607-611.

A 4bp-insertion in the eya-Homologous Region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10. / Pfister, Markus; Tóth, Tímea; Thiele, Holger; Haack, Birgit; Blin, Nikolaus; Zenner, Hans Peter; Sziklai, I.; Nürnberg, Peter; Kupka, Susan.

In: Molecular Medicine, Vol. 8, No. 10, 01.10.2002, p. 607-611.

Research output: Contribution to journalArticle

Pfister, M, Tóth, T, Thiele, H, Haack, B, Blin, N, Zenner, HP, Sziklai, I, Nürnberg, P & Kupka, S 2002, 'A 4bp-insertion in the eya-Homologous Region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10', Molecular Medicine, vol. 8, no. 10, pp. 607-611.
Pfister, Markus ; Tóth, Tímea ; Thiele, Holger ; Haack, Birgit ; Blin, Nikolaus ; Zenner, Hans Peter ; Sziklai, I. ; Nürnberg, Peter ; Kupka, Susan. / A 4bp-insertion in the eya-Homologous Region (eyaHR) of EYA4 causes hearing impairment in a Hungarian family linked to DFNA10. In: Molecular Medicine. 2002 ; Vol. 8, No. 10. pp. 607-611.
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