Abstract
Nonsyndromic hearing impairment is one of the most heterogeneous hereditary conditions, with more than 40 loci mapped on the human genome1, however, only a limited number of genes implicated in hearing loss have been identified. We previously reported linkage to chromosome 7p15 for autosomal dominant hearing impairment segregating in an extended Dutch family2,3 (DFNA5). Here, we report a further refinement of the DFNA5 candidate region and the isolation of a gene from this region that is expressed in the cochlea. In intron 7 of this gene, we identified an insertion/deletion mutation that does not affect intron-exon boundaries, but deletes five G-triplets at the 3' end of the intron. The mutation co-segregated with deafness in the family and causes skipping of exon 8, resulting in premature termination of the open reading frame. As no physiological function could be assigned, the gene was designated DFNA5.
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Acknowledgements
The authors are grateful to all family members for their collaboration in this study. The adult mouse cochlear cDNA λ ZAP library was kindly provided by L. Hampton and J. Battey. We wish to thank F. Cremers for the Dutch control samples, B. Beverlo for the mouse telomere probes, E. Fransen for his suggestions concerning the nature of the mutation, E. Green for the BAC clones and S.-H. Correwyn for preparing figures. This study was supported by a grant from the University of Antwerp, and a grant from the Flemish Fonds voor Wetenschappelijk Onderzoek (FWO). G.V.C. holds a research position with the FWO. R.J.H.S. is supported in part by research grant R01 DC 03544.
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Laer, L., Huizing, E., Verstreken, M. et al. Nonsyndromic hearing impairment is associated with a mutation in DFNA5. Nat Genet 20, 194–197 (1998). https://doi.org/10.1038/2503
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DOI: https://doi.org/10.1038/2503
