Localization of the Gene for Autosomal Recessive Congenital Hereditary Endothelial Dystrophy (CHED2) to Chromosome 20 by Homozygosity Mapping

• Published in: Genomics (San Diego, Calif.) Vol. 61; no. 1; pp. 1 - 4
• Main Authors: Hand, Collette K., Harmon, Dawn L., Kennedy, Susan M., FitzSimon, J.Susan, Collum, Louis M.T., Parfrey, Nollaig A.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-10-1999; Elsevier
• Subjects: Biological and medical sciences; Chromosome Mapping; Chromosomes, Human, Pair 20; Consanguinity; Corneal Dystrophies, Hereditary - genetics; Diseases of cornea, anterior segment and sclera; Endothelium, Corneal; Female; Genes, Recessive; Genetic Linkage; Homozygote; Humans; Male; Medical sciences; Microsatellite Repeats; Ophthalmology; Pedigree; Genetic mapping; Human; Eye disease; Corneal dystrophy; Keratopathy; Chromosome F20; Congenital disease; Genetic disease
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1999.5920

Congenital hereditary endothelial dystrophy (CHED) is a corneal disorder that presents with diffuse bilateral corneal clouding. Vision may be severely impaired, and many patients require corneal transplantation. Both autosomal dominant (AD) and autosomal recessive (AR) forms of the disorder have been described. The gene responsible for AD CHED (HGMW-approved symbol CHED1) has been mapped to the pericentromeric region of chromosome 20. Investigating a large, consanguineous Irish pedigree with autosomal recessive CHED, we have previously excluded linkage to this AD CHED locus. We now describe a genome-wide search using homozygosity mapping and DNA pooling. Evidence of linkage to chromosome 20p was demonstrated with a maximum lod score of 9.30 at a recombination fraction of 0.0 using microsatellite marker D20S482. A region of homozygosity in all affected individuals was identified, narrowing the disease gene locus to an 8-cM region flanked by markers D20S113 and D20S882. This AR CHED (HGMW-approved symbol CHED2) disease gene locus is physically and genetically distinct from the AD CHED locus.