A Nonsense Mutation in a Novel Gene Is Associated With Retinitis Pigmentosa in a Family Linked to the RP1 Locus
| Autor: | Samuel G. Jacobson, Xavier Guillonneau, Christine A. Kozak, Michael Danciger, Artur V. Cideciyan, Natik I. Piriev, Debora B. Farber |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Candidate gene DNA Complementary Genetic Linkage DNA Mutational Analysis Molecular Sequence Data Nonsense mutation Mice Inbred Strains Locus (genetics) Biology Mice Exon Gene mapping Retinitis pigmentosa Genetics medicine Animals Humans Amino Acid Sequence Eye Proteins Molecular Biology Gene Polymorphism Single-Stranded Conformational Genetics (clinical) Family Health Chromosome Mapping Nuclear Proteins Sequence Analysis DNA General Medicine medicine.disease Molecular biology eye diseases Pedigree Muridae Genes Suppression subtractive hybridization Mutation Female sense organs Microtubule-Associated Proteins Retinitis Pigmentosa Chromosomes Human Pair 8 |
| Zdroj: | Human Molecular Genetics. 8:1541-1546 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | Retinitis pigmentosa (RP) represents a group of inherited human retinal diseases which involve degeneration of photoreceptor cells resulting in visual loss and often leading to blindness. In order to identify candidate genes for the causes of these diseases, we have been studying a pool of photoreceptor-specific cDNAs isolated by subtractive hybridization of mRNAs from normal and photoreceptorless rd mouse retinas. One of these cDNAs was of interest because it mapped to proximal mouse chromosome 1 in a region homo-logous to human 8q11-q13, the locus of autosomal dominant RP1. Therefore, using the mouse cDNA as probe, we cloned the human cDNA (hG28) and its corresponding gene and mapped it near to D8S509, which lies in the RP1 locus. This gene consists of four exons with an open reading frame of 6468 nt encoding a protein of 2156 amino acids with a predicted mass of 240 kDa. Given its chromosomal localization, we screened this gene for mutations in a large family affected with autosomal dominant RP previously linked to the RP1 locus. We found an R677X mutation that co-segregated with disease in the family and is absent from unaffected members and 100 unrelated controls. This mutation is predicted to lead to rapid degradation of hG28 mRNA or to the synthesis of a truncated protein lacking approximately 70% of its original length. Our results suggest that R677X is responsible for disease in this family and that the gene corresponding to hG28 is the RP1 gene. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|