Prevalence of mutations in eyeGENE probands with a diagnosis of autosomal dominant retinitis pigmentosa.
OBJECTIVE
To screen samples from patients with presumed autosomal dominant retinitis pigmentosa (adRP) for mutations in 12 disease genes as a contribution to the research and treatment goals of the National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE).


METHODS
DNA samples were obtained from eyeGENE. A total of 170 probands with an intake diagnosis of adRP were tested through enrollment in eyeGENE. The 10 most common genes causing adRP (IMPDH1, KLHL7, NR2E3, PRPF3/RP18, PRPF31/RP11, PRPF8/RP13, PRPH2/RDS, RHO, RP1, and TOPORS) were chosen for PCR-based dideoxy sequencing, along with the two X-linked RP genes, RPGR and RP2. RHO, PRPH2, PRPF31, RPGR, and RP2 were completely sequenced, while only mutation hotspots in the other genes were analyzed.


RESULTS
Disease-causing mutations were identified in 52% of the probands. The frequencies of disease-causing mutations in the 12 genes were consistent with previous studies.


CONCLUSIONS
The Laboratory for Molecular Diagnosis of Inherited Eye Disease at the University of Texas in Houston has thus far received DNA samples from 170 families with a diagnosis of adRP from the eyeGENE Network. Disease-causing mutations in autosomal genes were identified in 48% (81/170) of these families while mutations in X-linked genes accounted for an additional 4% (7/170). Of the 55 distinct mutations detected, 19 (33%) have not been previously reported. All diagnostic results were returned by eyeGENE to participating patients via their referring clinician. These genotyped samples along with their corresponding phenotypic information are also available to researchers who may request access to them for further study of these ophthalmic disorders. (ClinicalTrials.gov number, NCT00378742.).
Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas.
Lori S
LS
Sullivan
Sara J
SJ
Bowne
Melissa J
MJ
Reeves
Delphine
D
Blain
Kerry
K
Goetz
Vida
V
Ndifor
Sally
S
Vitez
Xinjing
X
Wang
Santa J
SJ
Tumminia
Stephen P
SP
Daiger
D000328:Adult; D004247:DNA / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D050172:Genes, X-Linked / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*
D005136:Eye Proteins; D004247:DNA
DNA sequencing; eyeGENE; inherited retinal diseases; mutation prevalences; retinitis pigmentosa