title: NGS-based Molecular diagnosis of 105 eyeGENE(®) probands with Retinitis Pigmentosa.
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(®).
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Zhongqi
authors.initials: Z
authors.lastname: Ge
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Kristen
authors.initials: K
authors.lastname: Bowles
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute/National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Goetz
authors.affiliation: Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Hendrik P N
authors.initials: HP
authors.lastname: Scholl
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute/National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Xinjing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Keqing
authors.initials: K
authors.lastname: Wang
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.|Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, USA.|The Verna and Marrs Mclean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA.|Structural and Computational Biology and molecular Biophysics Graduate Program, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003598:Cytoskeletal Proteins; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D025202:Molecular Diagnostic Techniques; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D017470:Receptors, Glutamate / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000175:diagnosis* / Q000235:genetics*
chemical_list: C417525:ADGRV1 protein, human; D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; C576075:GRM6 protein, human; D009363:Neoplasm Proteins; D043562:Receptors, G-Protein-Coupled; D017470:Receptors, Glutamate