Title
Amino acid 572 in TMC1: hot spot or critical functional residue for dominant mutations causing hearing impairmentAmino acid 572 in TMC1: hot spot or critical functional residue for dominant mutations causing hearing impairment
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Human molecular genetics
Publication type
article
Publication
New York, N.Y.,
Subject
Human medicine
Source (journal)
Journal of human genetics. - New York, N.Y.
Volume/pages
54(2009):3, p. 188-190
ISSN
1434-5161
ISI
000265356100009
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Two different missense mutations, p.D572N and p.D572H, affecting the same nucleotide and codon of the TMC1 gene were earlier reported to cause autosomal dominant hearing impairment at locus DFNA36 in two North American families. No other dominant mutations of human TMC1 have been published. We ascertained a third North American family segregating autosomal dominant nonsyndromic hearing impairment at the DFNA36 locus. We identified the p.D572N mutation of TMC1 co-segregating with hearing loss in our study family. A comparative haplotype analysis of linked single nucleotide polymorphisms and short tandem repeats in the two families segregating p.D572N was not consistent with a founder effect. These findings can be explained in two ways. Either nucleotide 1714 is a hot spot for mutations or, alternatively, missense mutations at this site confer a specific pathogenic gain-of-function or dominant-negative effect.
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