Title
Detection of rare nonsynonymous variants in TGFB1 in otosclerosis patientsDetection of rare nonsynonymous variants in TGFB1 in otosclerosis patients
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Translational Neurosciences (TNW)
Human molecular genetics
Faculteit Geneeskunde
Publication type
article
Publication
London,
Subject
Human medicine
Source (journal)
Annals of human genetics. - London, 1954, currens
Volume/pages
73(2009):2, p. 171-175
ISSN
0003-4800
1469-1809
ISI
000263448700006
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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-â1 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-â1 may contribute to susceptibility to otosclerosis
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