Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease
| Autor: | Jacque L. Duncan, Niamh B. Stover, Sharon B. Schwartz, Mohammad Othman, Barbara J. Jennings, K. Thiran Jayasundera, Richard G. Weleber, Alessandro Iannaccone, Karmen M Trzupek, Paul A. Sieving, Samuel G. Jacobson, John R. Heckenlively, Matthew Brumm, Sten Andréasson, Richard A. Lewis, Maria Laura Ciccarelli, Beverly M. Yashar, Kari Branham, Jean Bennett, Dianna K H Wheaton, Gerald A. Fishman, David G. Birch, Pelin Atmaca-Sonmez, Anand Swaroop, Athanasios J. Karoukis |
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| Rok vydání: | 2012 |
| Předmět: |
Retinal degeneration
Male DNA Mutational Analysis Biology Neurodegenerative medicine.disease_cause Eye Ophthalmology & Optometry Genetic analysis Medical and Health Sciences chemistry.chemical_compound Degenerative disease Rare Diseases GTP-Binding Proteins Clinical Research Retinitis pigmentosa medicine Genetics Humans 2.1 Biological and endogenous factors Registries Genetic Testing Sex Distribution Aetiology Eye Proteins Eye Disease and Disorders of Vision X-linked recessive inheritance Mutation Intracellular Signaling Peptides and Proteins Neurosciences Dystrophy Membrane Proteins Genetic Diseases X-Linked Retinal Articles X-Linked Biological Sciences medicine.disease eye diseases Random Amplified Polymorphic DNA Technique Pedigree chemistry Genetic Diseases Female Retinitis Pigmentosa |
| Zdroj: | Investigative ophthalmology & visual science, vol 53, iss 13 |
| Popis: | PURPOSE. To determine the proportion of male patients presenting simplex retinal degenerative disease (RD: retinitis pigmentosa [RP] or cone/cone-rod dystrophy [COD/CORD]) with mutations in the X-linked retinal degeneration genes RPGR and RP2. METHODS. Simplex males were defined as patients with no known affected family members. Patients were excluded if they had a family history of parental consanguinity. Blood samples from a total of 214 simplex males with a diagnosis of retinal degeneration were collected for genetic analysis. The patients were screened for mutations in RPGR and RP2 by direct sequencing of PCR-amplified genomic DNA. RESULTS. We identified pathogenic mutations in 32 of the 214 patients screened (15%). Of the 29 patients with a diagnosis of COD/CORD, four mutations were identified in the ORF15 mutational hotspot of the RPGR gene. Of the 185 RP patients, three patients had mutations in RP2 and 25 had RPGR mutations (including 12 in the ORF15 region). CONCLUSIONS. This study represents mutation screening of RPGR and RP2 in the largest cohort, to date, of simplex males affected with RP or COD/CORD. Our results demonstrate a substantial contribution of RPGR mutations to retinal degenerations, and in particular, to simplex RP. Based on our findings, we suggest that RPGR should be considered as a first tier gene for screening isolated males with retinal degeneration. (Invest Ophthalmol Vis Sci. 2012;53:8232-8237) DOI:10.1167/iovs.12-11025 (Less) |
| Databáze: | OpenAIRE |
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