Abstract
The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE®) was established in an effort to facilitate basic and clinical research of human inherited eye disease. In order to provide high quality genetic testing to eyeGENE®’s enrolled patients which potentially aids clinical diagnosis and disease treatment, we carried out a pilot study and performed Next-generation sequencing (NGS) based molecular diagnosis for 105 Retinitis Pigmentosa (RP) patients randomly selected from the network. A custom capture panel was designed, which incorporated 195 known retinal disease genes, including 61 known RP genes. As a result, disease-causing mutations were identified in 52 out of 105 probands (solving rate of 49.5%). A total of 82 mutations were identified, and 48 of them were novel. Interestingly, for three probands the molecular diagnosis was inconsistent with the initial clinical diagnosis, while for five probands the molecular information suggested a different inheritance model other than that assigned by the physician. In conclusion, our study demonstrated that NGS target sequencing is efficient and sufficiently precise for molecular diagnosis of a highly heterogeneous patient cohort from eyeGENE®.
Highlights
Retinitis Pigmentosa (RP) is the most common form of inherited retinal degeneration, which has an estimated prevalence of 1 in 3,500–4,000 individuals[1]
The traditional diagnostic test for genetic and allelic heterogeneous diseases such as RP has been limited to Sanger sequencing and arrayed primer extension (APEX)[7]
Next-generation sequencing (NGS) based genetic testing is gradually being adopted as the method of choice for molecular diagnosis of RP patients, 1Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA. 2Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA. 3Ophthalmic Genetics and Visual Function Branch, National Eye Institute/National Institutes of Health, Bethesda, Maryland, USA. 4Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA. 5Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA. 6The Verna and Marrs Mclean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA. 7Structural and Computational Biology and molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, Texas, USA
Summary
Retinitis Pigmentosa (RP) is the most common form of inherited retinal degeneration, which has an estimated prevalence of 1 in 3,500–4,000 individuals[1]. NGS based genetic testing is gradually being adopted as the method of choice for molecular diagnosis of RP patients, 1Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA. Through NGS based sequencing analysis we assigned causative mutations to 52 patients, achieving a solving rate of 49.5%.
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