Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease.

Abstract

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.

• Authors: Kari Branham, Mohammad Othman, Matthew Brumm, Athanasios J Karoukis, Pelin Atmaca-Sonmez, Beverly M Yashar, Sharon B Schwartz, Niamh B Stover, Karmen Trzupek, Dianna Wheaton, Barbara Jennings, Maria Laura Ciccarelli, K Thiran Jayasundera, Richard A Lewis, David Birch, Jean Bennett, Paul A Sieving, Sten Andreasson, Jacque L Duncan, Gerald A Fishman, Alessandro Iannaccone, Richard G Weleber, Samuel G Jacobson, John R Heckenlively, Anand Swaroop
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 53 Issue 13 Pg. 8232-7 (Dec 13 2012) ISSN: 1552-5783 [Electronic] United States
• PMID: 23150612 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Eye Proteins
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• RP2 protein, human
• RPGR protein, human
• GTP-Binding Proteins

Topics

• DNA Mutational Analysis
• Eye Proteins (genetics)
• Female
• GTP-Binding Proteins
• Genetic Diseases, X-Linked (diagnosis, genetics)
• Genetic Testing
• Humans
• Intracellular Signaling Peptides and Proteins (genetics)
• Male
• Membrane Proteins (genetics)
• Mutation
• Pedigree
• Random Amplified Polymorphic DNA Technique
• Registries
• Retinitis Pigmentosa (diagnosis, genetics)
• Sex Distribution