Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus.
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State: Public
Version: Final published version
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It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
State: Public
Version: Final published version
License: Not specified
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Serval ID
serval:BIB_8CB564BB9994
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus.
Journal
Human Molecular Genetics
ISSN
1460-2083 (Electronic)
ISSN-L
0964-6906
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
23
Number
20
Pages
5527-35
Language
english
Notes
Publication types: JOURNAL ARTICLE
Abstract
Keratoconus, a common inherited ocular disorder resulting in progressive corneal thinning, is the leading indication for corneal transplantation in the developed world. Genome-wide association studies have identified common SNPs 100 kb upstream of ZNF469 strongly associated with corneal thickness. Homozygous mutations in ZNF469 and PR domain-containing protein 5 (PRDM5) genes result in brittle cornea syndrome (BCS) Types 1 and 2, respectively. BCS is an autosomal recessive generalized connective tissue disorder associated with extreme corneal thinning and a high risk of corneal rupture. Some individuals with heterozygous PRDM5 mutations demonstrate a carrier ocular phenotype, which includes a mildly reduced corneal thickness, keratoconus and blue sclera. We hypothesized that heterozygous variants in PRDM5 and ZNF469 predispose to the development of isolated keratoconus. We found a significant enrichment of potentially pathologic heterozygous alleles in ZNF469 associated with the development of keratoconus (P = 0.00102) resulting in a relative risk of 12.0. This enrichment of rare potentially pathogenic alleles in ZNF469 in 12.5% of keratoconus patients represents a significant mutational load and highlights ZNF469 as the most significant genetic factor responsible for keratoconus identified to date.
Pubmed
Web of science
Open Access
Yes
Create date
11/09/2014 8:52
Last modification date
14/02/2022 8:56