Related resources
Full-text held externally
- PMID: 24895405
- UKPMCID: 24895405
- DOI: 10.1093/hmg/ddu253
Search for item elsewhere
University researcher(s)
Academic department(s)
Enrichment of pathogenic alleles in the brittle cornea gene, ZNF469, in keratoconus.
Lechner, Judith; Porter, Louise F; Rice, Aine; Vitart, Veronique; Armstrong, David J; Schorderet, Daniel F; Munier, Francis L; Wright, Alan F; Inglehearn, Chris F; Black, Graeme C; Simpson, David A; Manson, Forbes; Willoughby, Colin E
Human molecular genetics. 2014;23(20):5527-35.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
- PMID: 24895405
- UKPMCID: 24895405
- DOI: 10.1093/hmg/ddu253
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.