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Lori S. Sullivan, Sara J. Bowne, Delphine Blain, Kerry Goetz, Vida Ndifor, Melissa Reeves, Sally Vitez, Santa J. Tumminia, Stephen P. Daiger; Prevalence of Mutations in eyeGENE® Probands With Autosomal Dominant Retinitis Pigmentosa or Inherited Maculopathy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4546.
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To systematically screen samples from patients with autosomal dominant retinitis pigments (adRP) and various inherited maculopathies for mutations in 11 disease genes: RHO, PRPH2 (RDS), RP1, IMPDH1, PRPF3, PRPF8, PRPF31, NR2E3, TOPORS, KLHL7, RPGR and RP2.
DNA samples were obtained from the National Eye Institute - National Ophthalmic Genotyping and Phenotyping Network (eyeGENE®). A total of 171 probands with an intake diagnosis of autosomal dominant retinitis pigmentosa and 96 probands with a diagnosis of pattern dystrophy or complex maculopathy were selected. The nine most common genes causing adRP were chosen for PCR-based dideoxy sequencing along with the two X-linked genes, RPGR and RP2, which can cause disease in apparent "dominant" families. RHO, PRPH2 (RDS), PRPF31, RPGR and RP2 were completely sequenced while only mutation hotspots in the other genes were analyzed. Patients with a diagnosis of inherited maculopathy were only screened for mutations in PRPH2.
Overall, disease-causing mutations were identified in 51.5% of probands with adRP and in 23% of probands with inherited maculopathy. In adRP samples, the frequencies of disease-causing mutations in the 11 genes were consistent with previous studies. Mutations in rhodopsin accounted for 26% (45/171), RP1 - 6% (10/171), PRPF31 - 5% (8/171), PRPH2 - 4% (7/171), RPGR - 6% (6/171), PRPF8 - 3% (5/171), TOPORS - 2% (3/171), IMPDH1 - 1% (2/171), and NR2E3 - 0.5% (1/171). No mutations were identified in either KLHL7 or RP2.
The eyeGENE® Network is a national genetics initiative whose fundamental purpose is to foster and support research into the genetic causes of ophthalmic disorders. This is accomplished by broadening patient and family access to genetic diagnostic testing and by creating and maintaining a national repository of genetic samples from highly characterized individuals and families. The Network, officially launched in 2006, is a component of the NEI Intramural Research Program, and is a model partnership between the federal government, eye health care providers, CLIA-approved molecular diagnostic laboratories, private industry, and extramural scientists who support a broad research constituency. Since testing began in 2007, the Laboratory for the Diagnosis of Inherited Eye Disease at the University of Texas Health Science Center at Houston has received 326 DNA samples from 277 families, including the families in this report. Disease-causing mutations in autosomal genes were identified in 47% (81/171) of the families with RP while mutations in X-linked genes accounted for an additional 4% (6/171). In families with an inherited maculopathy, 23% were found to have mutations in PRPH2.
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