title: Exclusion of AR-CHED from the chromosome 20 region containing the PPMD and AD-CHED loci.
abstract: Congenital hereditary endothelial dystrophy (CHED) is a disorder of the corneal endothelium and has been recognized to segregate in families with both autosomal dominant (AD) and autosomal recessive (AR) modes of transmission. AD-CHED has been previously linked to the pericentric region of chromosome 20. Posterior polymorphous dystrophy (PPMD), a corneal endothelial disorder showing phenotypic overlap with CHED, has also been previously genetically mapped to this region. The genetic interval containing AD-CHED is within the larger genetic interval containing the PPMD locus. This study sought to determine whether AR-CHED segregating in a consanguineous Saudi Arabian pedigree is linked to the previously mapped and overlapping loci for AD-CHED and PPMD on the pericentric region of chromosome 20. Forty members of a consanguineous Saudi Arabian pedigree segregating AR-CHED were ascertained. Short tandem-repeat polymorphic markers from the 20 cM interval on chromosome 20 containing both the PPMD and AD-CHED loci were used to genotype these individuals. LOD score analysis of the genotype data with the MENDEL software package utilizing a model of autosomal recessive inheritance with complete penetrance showed exclusion of CHED from the entire PPMD/AD-CHED interval by utilizing overlapping intervals of LOD scores of at least -2. The results obtained demonstrate that AR-CHED is not allelic to either AD-CHED or PPMD, although it has been proposed that AD-CHED may be allelic to PPMD. Thus, there are at least two genes responsible for CHED and PPMD.
authors.affiliation: Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Kanis
authors.forename: A A
authors.initials: AA
authors.lastname: Al-Rajhi
authors.forename: C M
authors.initials: CM
authors.lastname: Taylor
authors.forename: W D
authors.initials: WD
authors.lastname: Mathers
authors.forename: R Y
authors.initials: RY
authors.lastname: Folberg
authors.forename: D Y
authors.initials: DY
authors.lastname: Nishimura
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D003316:Corneal Diseases / Q000235:genetics* / Q000473:pathology; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology; D004728:Endothelium, Corneal / Q000002:abnormalities*; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree