Detection of rare nonsynonymous variants in TGFB1 in otosclerosis patients

M Thys; I Schrauwen; K Vanderstraeten; N Dieltjens; E Fransen; M Ealy; C W R J Cremers; P van de Heyning; R Vincent; E Offeciers; R H Smith; G van Camp

doi:10.1111/j.1469-1809.2009.00505.x

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Detection of rare nonsynonymous variants in TGFB1 in otosclerosis patients

Journal article

Peer reviewed

Detection of rare nonsynonymous variants in TGFB1 in otosclerosis patients

M Thys, I Schrauwen, K Vanderstraeten, N Dieltjens, E Fransen, M Ealy, C W R J Cremers, P van de Heyning, R Vincent, E Offeciers, …

Annals of human genetics, Vol.73(2), pp.171-175

03/2009

DOI: 10.1111/j.1469-1809.2009.00505.x

PMID: 19207109

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Abstract

Otosclerosis is one of the most common forms of hearing loss in the European population. We have identified a SNP in the TGFB1 (transforming growth factor beta 1) gene that is associated with susceptibility to otosclerosis. The protective allele of this variant, with isoleucine at position 263 of the protein, is more biologically active than the risk allele, which has a threonine in this position. Because recent studies have shown that not only common, but also rare variants can be involved in complex diseases, we performed DNA sequence analysis of the exons and intron-exon boundaries of TGFB1 in 755 otosclerosis patients and 877 control samples. We found 3 different nonsynonymous variants (E29, A29 and I241) in four otosclerosis patients, but no such changes were found in controls. In silico analysis shows that these variations could influence TGF-beta1 function and activity. Taking into account that most rare missense alleles are thought to have a biological effect, the data suggest that multiple rare amino acid changing variants in TGF-beta1 may contribute to susceptibility to otosclerosis.

Europe

Genetic Predisposition to Disease

DNA Mutational Analysis

Humans

Female

Male

Otosclerosis - genetics

Transforming Growth Factor beta1 - genetics

Mutation, Missense

Case-Control Studies

Details

Title: Subtitle: Detection of rare nonsynonymous variants in TGFB1 in otosclerosis patients
Creators: M Thys - Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, Antwerp, Belgium
I Schrauwen
K Vanderstraeten
N Dieltjens
E Fransen
M Ealy
C W R J Cremers
P van de Heyning
R Vincent
E Offeciers
R H Smith
G van Camp
Resource Type: Journal article
Publication Details: Annals of human genetics, Vol.73(2), pp.171-175
DOI: 10.1111/j.1469-1809.2009.00505.x
PMID: 19207109
NLM abbreviation: Ann Hum Genet
ISSN: 1469-1809
eISSN: 1469-1809
Publisher: England
Language: English
Date published: 03/2009
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984007175302771

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