Mutations in RPGR and RP2 Account for 15% of Males with Simplex Retinal Degenerative Disease

Department of Ophthalmology and Visual Sciences, University of Michigan, Kellogg Eye Center, Ann Arbor, MI, 48105, United States.
Investigative ophthalmology & visual science (Impact Factor: 3.43). 11/2012; 53(13). DOI: 10.1167/iovs.12-11025
Source: PubMed

ABSTRACT PURPOSE: To determine the proportion of male patients presenting as 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, 3 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 affected with retinal degeneration.

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May 15, 2014