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- Title
DFNA54, a third locus for low-frequency hearing loss.
- Authors
Gürtler, Nicolas; Kim, Yuil; Mhatre, Anand; Schlegel, Christoph; Mathis, Alfons; Lalwani, Anil K.
- Abstract
Nonsyndromic hereditary hearing impairment (NSHHI) is a highly heterogeneous disorder with more than 90 loci mapped, of which nearly one-half of the responsible genes are identified. In dominant NSSHI hearing loss is typically biased towards the high frequencies while low-frequency hearing loss is unusual. Only two NSHHI loci, DFNA1 and DFNA6/14/38, are associated with predominantly low- frequency loss. We mapped the loci harboring the gene responsible for autosomal dominant low-frequency hearing loss in a multigenerational family. The pedigree of a Swiss family with low-frequency hearing loss was established. Using genomic DNA, DFNA1 and DFNA6/14/38 were excluded by linkage analysis or by direct sequencing of the responsible gene. Genome-wide linkage analysis was performed using commercially available microsatellite markers. Two-point linkage analysis demonstrated linkage to chromosome 5q31, the locus for DFNA15, with a lod score of 6.32 at recombination fraction ?=0 for marker D5S436. Critical recombinations were seen at markers D5S1972 and D5S410. Sequencing of the corresponding genePOU4F3yielded no pathogenic mutation segregating with the affected members. In addition to Wolfram syndrome gene 1 (DFNA6/14/38) and diaphanous (DFNA1) there is evidence for a third gene involved in low-frequency hearing loss located at DFNA15. Because of the differences in auditory phenotype and the absence of pathogenic mutation in the coding region ofPOU4F3it is likely that there is a second gene in 5q31, designated DFNA54, associated with NSHHI.
- Subjects
HEARING disorders; GENOMICS; CHROMOSOMES; MICROSATELLITE repeats; HUMAN genetics
- Publication
Journal of Molecular Medicine, 2004, Vol 82, Issue 11, p775
- ISSN
0946-2716
- Publication type
Article
- DOI
10.1007/s00109-004-0597-1