DFNA8/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss
| Autor: | Hannie Kremer, Guy Van Camp, Katherine Lachlan, Isabelle Schrauwen, Thomas L. Casavant, Leticia Olavarrieta, Adam P. DeLuca, Carla Nishimura, Bruce W. Tompkins, Carmelo Morales-Angulo, Fernando Mayo, Patrick L. M. Huygen, Richard J.H. Smith, Ignacio del Castillo, Maarten Van Wesemael, Terry A. Braun, Felipe Moreno, Michael S. Hildebrand, Kyle R. Taylor, Ángeles Mencía, Silvia Modamio-Høybjør, M A Moreno-Pelayo, Matías Morín, A. Eliot Shearer, Corey W. Goodman, Nicole C. Meyer, Heather Workman |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Proband
Adult Male Adolescent Hearing loss Genetic Linkage Hearing Loss Sensorineural Population Biology medicine.disease_cause GPI-Linked Proteins Article 03 medical and health sciences 0302 clinical medicine Audiometry Genetics medicine Missense mutation Humans TECTA education Child Genetics (clinical) Genetic Association Studies 030304 developmental biology Aged 0303 health sciences Mutation education.field_of_study Extracellular Matrix Proteins Haplotype Middle Aged Glycostation disorders [IGMD 4] Founder Effect Pedigree Protein Structure Tertiary Haplotypes Child Preschool Genetics and epigenetic pathways of disease Functional Neurogenomics [NCMLS 6] Female Human medicine medicine.symptom 030217 neurology & neurosurgery Founder effect |
| Zdroj: | Human Mutation, 32, 7, pp. 825-34 Human mutation Human Mutation, 32, 825-34 |
| ISSN: | 1059-7794 |
| Popis: | Item does not contain fulltext 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 alpha-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 alpha-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text