title: Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity.
abstract: Recently Dryja and his co-workers observed a mutation in the 23d codon of the rhodopsin gene in a proportion of autosomal dominant retinitis pigmentosa (ADRP) patients. Linkage analysis with a rhodopsin-linked probe C17 (D3S47) was carried out in two large British ADRP families, one with diffuse-type (D-type) RP and the other with regional-type (R-type) RP. Significantly positive lod scores (lod score maximum [Zmax] = +5.58 at recombination fraction [theta] = .0) were obtained between C17 and our D-type ADRP family showing complete penetrance. Sequence and oligonucleotide analysis has, however, shown that no point mutation at the 23d codon exists in affected individuals in our complete-penetrance pedigree, indicating that another rhodopsin mutation is probably responsible for ADRP in this family. Significantly negative lod scores (Z less than -2 at theta = .045) were, however, obtained between C17 and our R-type family which showed incomplete penetrance. Previous results presented by this laboratory also showed no linkage between C17 and another large British R-type ADRP family with incomplete penetrance. This confirms genetic heterogeneity. Some types of ADRP are being caused by different mutations in the rhodopsin locus (3q21-24) or another tightly linked gene in this region, while other types of ADRP are the result of mutations elsewhere in the genome.
authors.affiliation: Department of Human Genetics, University of Newcastle upon Tyne, England.
authors.forename: D H
authors.initials: DH
authors.lastname: Lester
authors.forename: C F
authors.initials: CF
authors.lastname: Inglehearn
authors.forename: R
authors.initials: R
authors.lastname: Bashir
authors.forename: H
authors.initials: H
authors.lastname: Ackford
authors.forename: L
authors.initials: L
authors.lastname: Esakowitz
authors.forename: M
authors.initials: M
authors.lastname: Jay
authors.forename: A C
authors.initials: AC
authors.lastname: Bird
authors.forename: A F
authors.initials: AF
authors.lastname: Wright
authors.forename: S S
authors.initials: SS
authors.lastname: Papiha
authors.forename: S S
authors.initials: SS
authors.lastname: Bhattacharya
mesh_terms: D001483:Base Sequence; D003062:Codon; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D014644:Genetic Variation; D006801:Humans; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012168:Retinal Pigments / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012243:Rhodopsin / Q000235:genetics*
chemical_list: D003062:Codon; D012168:Retinal Pigments; D012243:Rhodopsin