Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11) and association with a unique bimodal expressivity phenotype.
- 1 October 1996
- journal article
- Vol. 59 (4) , 864-71
Abstract
Retinitis pigmentosa (RP) is the name given to a heterogeneous group of retinal degenerations mapping to at least 16 loci. The autosomal dominant form (ARP), accounting for approximately 25% of cases, can be caused by mutations in two genes, rhodopsin and peripherin/RDS, and by at least six other loci identified by linkage analysis. The RP11 locus for adRP has previously been mapped to chromosome 19q13.4 in a large English family. This linkage has been independently confirmed in a Japanese family, and we now report three additional unrelated linked U.K. families, suggesting that this is a major locus for RP. Linkage analysis in the U.K. families refines the RP11 interval to 5 cM between markers D19S180 and AFMc001yb1. All linked families exhibit incomplete penetrance; some obligate gene carriers remain asymptomatic throughout their lives, whereas symptomatic individuals experience night blindness and visual field loss in their teens and are generally registered as blind by their 30s. This "bimodal expressivity" contrasts with the variable-expressivity RP mapping to chromosome 7p (RP9) in another family, which has implications for diagnosis and counseling of RP11 families. These results may also imply that a proportion of sporadic RP, previously assumed to be recessive, might result from mutations at this locus.This publication has 25 references indexed in Scilit:
- Digenic Retinitis Pigmentosa Due to Mutations at the Unlinked Peripherin/ RDS and ROM1 LociScience, 1994
- A new locus for autosomal dominant retinitis pigmentosa on the short arm of chromosome 17Human Molecular Genetics, 1994
- The 1993–94 Généthon human genetic linkage mapNature Genetics, 1994
- Genetic linkage of cone–rod retinal dystrophy to chromosome 19q and evidence for segregation distortionNature Genetics, 1994
- Identification of a sixth locus for autosomal dominant retinitis pigmentosa on chromosome 19Human Molecular Genetics, 1994
- Autosomal dominant retinitis pigmentosa with apparent incomplete penetrance: a clinical, electrophysiological, psychophysical, and molecular genetic study.British Journal of Ophthalmology, 1993
- A new locus for autosomal dominant retinitis pigmentosa on chromosome 7pNature Genetics, 1993
- Localization of an autosomal dominant retinitis pigmentosa gene to chromosome 7qNature Genetics, 1993
- The UK Human Genome Mapping Project online computing serviceBioinformatics, 1992
- Linkage mapping of autosomal dominant retinitis pigmentosa (RP1) to the pericentric region of human chromosome 8Genomics, 1991