TY - JOUR
T1 - Mutations in RPGR and RP2 account for 15% of males with simplex retinal degenerative disease
AU - Branham, Kari
AU - Othman, Mohammad
AU - Brumm, Matthew
AU - Karoukis, Athanasios J.
AU - Atmaca-Sonmez, Pelin
AU - Yashar, Beverly M.
AU - Schwartz, Sharon B.
AU - Stover, Niamh B.
AU - Trzupek, Karmen
AU - Wheaton, Dianna
AU - Jennings, Barbara
AU - Ciccarelli, Maria Laura
AU - Thiran Jayasundera, K.
AU - Lewis, Richard A.
AU - Birch, David
AU - Bennett, Jean
AU - Sieving, Paul A.
AU - Andreasson, Sten
AU - Duncan, Jacque L.
AU - Fishman, Gerald A.
AU - Iannaccone, Alessandro
AU - Weleber, Richard G.
AU - Jacobson, Samuel G.
AU - Heckenlively, John R.
AU - Swaroop, Anand
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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.
AB - 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.
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U2 - 10.1167/iovs.12-11025
DO - 10.1167/iovs.12-11025
M3 - Article
C2 - 23150612
AN - SCOPUS:84873328062
VL - 53
SP - 8232
EP - 8237
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 13
ER -