Homozygosity mapping and linkage analysis demonstrate that autosomal recessive congenital hereditary endothelial dystrophy (CHED) and autosomal dominant CHED are genetically distinct

• Published in: British journal of ophthalmology Vol. 83; no. 1; pp. 115 - 119
• Main Authors: Callaghan, Máire, Hand, Collette K, Kennedy, Susan M, FitzSimon, J Susan, Collum, Louis M T, Parfrey, Nollaig A
• Format: Journal Article
• Language: English
• Published: BMA House, Tavistock Square, London, WC1H 9JR BMJ Publishing Group Ltd 01-01-1999; BMJ; BMJ Publishing Group LTD
• Subjects: Biological and medical sciences; Chromosome Mapping; Congenital diseases; congenital hereditary endothelial dystrophy; Corneal Dystrophies, Hereditary - genetics; Defects; Deoxyribonucleic acid; Disease; Diseases of cornea, anterior segment and sclera; DNA; Female; Genes; Genetic testing; Genomes; homozygosity mapping; Homozygote; Humans; linkage analysis; Male; Medical sciences; Microsatellite Repeats; Ophthalmology; Original articles - Laboratory science; Pedigree; Polymorphism, Genetic; posterior polymorphous dystrophy; Human; Linkage; Congenital; Family study; Keratopathy; Homozygosity; Hereditary; Congenital disease; Genetic determinism; Differential diagnostic; Genetic disease; Polymerase chain reaction; Eye disease; Corneal dystrophy; Autosomal character; Dominant character
• ISSN: 0007-1161; 1468-2079
• DOI: 10.1136/bjo.83.1.115

BACKGROUND Congenital hereditary endothelial dystrophy (CHED) is a corneal dystrophy characterised by diffuse bilateral corneal clouding resulting in impaired vision. It is inherited in either an autosomal dominant (AD) or autosomal recessive (AR) manner. The AD form of CHED has been mapped to the pericentromeric region of chromosome 20. Another endothelial dystrophy, posterior polymorphous dystrophy (PPM), has been linked to a larger but overlapping region on chromosome 20. A large, Irish, consanguineous family with AR CHED was investigated to determine if there was linkage to this region. METHODS The technique of linkage analysis with polymorphic microsatellite markers amplified by polymerase chain reaction (PCR) was used. In addition, a DNA pooling approach to homozygosity mapping was employed to demonstrate the efficiency of this method. RESULTS Conventional genetic analysis in addition to a pooled DNA strategy excludes linkage of AR CHED to the AD CHED and larger PPMD loci. CONCLUSION This demonstrates that AR CHED is genetically distinct from AD CHED and PPMD.