Journal article
DFNA8/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss
Human mutation, Vol.32(7), pp.825-834
07/2011
DOI: 10.1002/humu.21512
PMCID: PMC3326665
PMID: 21520338
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 D1-D2 and TIL2 connectors. Although the majority are private mutations, four of them-p.Cys1036Tyr, p.Cys1837Gly, p.Thr1866Met, and p.Arg1890Cys-were observed in more than one unrelated family. For two of these mutations founder effects were also confirmed. Our data validate previously observed genotype-phenotype 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.
Details
- Title: Subtitle
- DFNA8/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss
- Creators
- Michael S Hildebrand - Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA 52242, USAMatías MorínNicole C MeyerFernando MayoSilvia Modamio-HoybjorAngeles MencíaLeticia OlavarrietaCarmelo Morales-AnguloCarla J NishimuraHeather WorkmanAdam P DeLucaIgnacio del CastilloKyle R TaylorBruce TompkinsCorey W GoodmanIsabelle SchrauwenMaarten Van WesemaelK LachlanA Eliot ShearerTerry A BraunPatrick L M HuygenHannie KremerGuy Van CampFelipe MorenoThomas L CasavantRichard J H SmithMiguel A Moreno-Pelayo
- Resource Type
- Journal article
- Publication Details
- Human mutation, Vol.32(7), pp.825-834
- DOI
- 10.1002/humu.21512
- PMID
- 21520338
- PMCID
- PMC3326665
- NLM abbreviation
- Hum Mutat
- ISSN
- 1059-7794
- eISSN
- 1098-1004
- Publisher
- United States
- Grant note
- R01 DC003544-14 / NIDCD NIH HHS R01 DC003544 / NIDCD NIH HHS GM082729 / NIGMS NIH HHS T32 GM082729 / NIGMS NIH HHS DC003544 / NIDCD NIH HHS T32 GM007337 / NIGMS NIH HHS
- Language
- English
- Date published
- 07/2011
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Center for Bioinformatics and Computational Biology; Otolaryngology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984006485302771
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