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

Branham, Kari; Othman, Mohammad; Brumm, Matthew; Karoukis, Athanasios J.; Atmaca-Sonmez, Pelin; Yashar, Beverly M.; Schwartz, Sharon B.; Stover, Niamh B.; Trzupek, Karmen and Wheaton, Dianna, et al. (2012) In Investigative Ophthalmology & Visual Science 53(13). p.8232-8237
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... (More)
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)
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Investigative Ophthalmology & Visual Science
volume
53
issue
13
pages
8232 - 8237
publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
external identifiers
  • wos:000313056000043
  • scopus:84873328062
ISSN
1552-5783
DOI
10.1167/iovs.12-11025
language
English
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yes
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c219964b-c238-40b6-8eca-dbdc48b0b73a (old id 3508068)
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2013-03-01 07:51:55
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2017-08-13 03:58:18
@article{c219964b-c238-40b6-8eca-dbdc48b0b73a,
  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. (Invest Ophthalmol Vis Sci. 2012;53:8232-8237) DOI:10.1167/iovs.12-11025},
  author       = {Branham, Kari and Othman, Mohammad and Brumm, Matthew and Karoukis, Athanasios J. and Atmaca-Sonmez, Pelin and Yashar, Beverly M. and Schwartz, Sharon B. and Stover, Niamh B. and Trzupek, Karmen and Wheaton, Dianna and Jennings, Barbara and Ciccarelli, Maria Laura and Jayasundera, K. Thiran and Lewis, Richard A. and Birch, David and Bennett, Jean and Sieving, Paul A. and Andréasson, Sten and Duncan, Jacque L. and Fishman, Gerald A. and Iannaccone, Alessandro and Weleber, Richard G. and Jacobson, Samuel G. and Heckenlively, John R. and Swaroop, Anand},
  issn         = {1552-5783},
  language     = {eng},
  number       = {13},
  pages        = {8232--8237},
  publisher    = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
  series       = {Investigative Ophthalmology & Visual Science},
  title        = {Mutations in RPGR and RP2 Account for 15% of Males with Simplex Retinal Degenerative Disease},
  url          = {http://dx.doi.org/10.1167/iovs.12-11025},
  volume       = {53},
  year         = {2012},
}