A novel DFNA5 mutation does not cause hearing loss in an Iranian family

Mutations in DFNA5 lead to autosomal dominant non-syndromic sensorineural hearing loss that starts at the high frequencies. To date, only three DFNA5 mutations have been described, and although different at the genomic DNA level, all lead to exon 8 skipping at the mRNA level. This remarkable fact ha...

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Bibliographic Details
Published inJournal of human genetics Vol. 52; no. 6; pp. 549 - 552
Main Authors Van Laer, Lut, Meyer, Nicole C, Malekpour, Mahdi, Riazalhosseini, Yasser, Moghannibashi, Mahdi, Kahrizi, Kimia, Vandevelde, Ann, Alasti, Fatemeh, Najmabadi, Hossein, Van Camp, Guy, Smith, Richard J H
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.06.2007
Subjects
Cohort Studies
Cytosine
DNA Mutational Analysis
Female
Frameshift mutation
Hearing loss
Hearing Loss, Sensorineural - genetics
Hearing protection
Humans
Hypotheses
Iran
Male
mRNA
Mutation
Pedigree
Phenotypes
Receptors, Estrogen - genetics
Iran
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Summary:Mutations in DFNA5 lead to autosomal dominant non-syndromic sensorineural hearing loss that starts at the high frequencies. To date, only three DFNA5 mutations have been described, and although different at the genomic DNA level, all lead to exon 8 skipping at the mRNA level. This remarkable fact has led towards the hypothesis that DFNA5-associated hearing loss is caused by a gain-of-function mutation and not by haplo-insufficiency as previously thought. Here, we describe a fourth DFNA5 mutation: the insertion of a cytosine at nucleotide position 640 (AF073308.1:_c.640insC, AAC69324.1:_p. Thr215HisfsX8). Unlike the previously described mutations, this frameshift mutation truncates the protein in exon 5 of the gene. Although the mutation was found in an extended Iranian family with hereditary hearing loss, it does not segregate with the hearing loss phenotype and is even present in persons with normal hearing. This fact provides further support for the hypothesis that DFNA5-associated hearing loss is caused by a gain-of-function mutation.
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ISSN:1434-5161
1435-232X
DOI:10.1007/s10038-007-0137-2