Publication
Title
DFNA8/12 caused by **TECTA** mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss
Author
Abstract
The prevalence of DFNA8/DFNA12 (DFNA8/12), a type of autosomal dominant nonsyndromic hearing loss (ADNSHL), is unknown as comprehensive population-based genetic screening has not been conducted. We therefore completed unbiased screening for TECTA mutations in a Spanish cohort of 372 probands from ADNSHL families. Three additional families (Spanish, Belgian, and English) known to be linked to DFNA8/12 were also included in the screening. In an additional cohort of 835 American ADNSHL families, we preselected 73 probands for TECTA screening based on audiometric data. In aggregate, we identified 23 TECTA mutations in this process. Remarkably, 20 of these mutations are novel, more than doubling the number of reported TECTA ADNSHL mutations from 13 to 33. Mutations lie in all domains of the α-tectorin protein, including those for the first time identified in the entactin domain, as well as the vWFD1, vWFD2, and vWFD3 repeats, and the D1D2 and TIL2 connectors. Although the majority are private mutations, four of themp.Cys1036Tyr, p.Cys1837Gly, p.Thr1866Met, and p.Arg1890Cyswere observed in more than one unrelated family. For two of these mutations founder effects were also confirmed. Our data validate previously observed genotypephenotype correlations in DFNA8/12 and introduce new correlations. Specifically, mutations in the N-terminal region of α-tectorin (entactin domain, vWFD1, and vWFD2) lead to mid-frequency NSHL, a phenotype previously associated only with mutations in the ZP domain. Collectively, our results indicate that DFNA8/12 hearing loss is a frequent type of ADNSHL.
Language
English
Source (journal)
Human mutation. - New York, N.Y.
Publication
New York, N.Y. : 2011
ISSN
1059-7794
Volume/pages
32:7(2011), p. 825-834
ISI
000292551800015
Full text (Publishers DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 30.08.2011
Last edited 13.04.2017
To cite this reference