Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus.

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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
Author(s)
Lechner J., Porter L.F., Rice A., Vitart V., Armstrong D.J., Schorderet D.F., Munier F.L., Wright A.F., Inglehearn C.F., Black G.C., Simpson D.A., Manson F., Willoughby C.E.
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
25/09/2019 7:09
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