Clinical ophthalmic molecular diagnostics and discovery

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The Ophthalmic Genetics Laboratory. was designed to gather and manage biospecimens and molecular diagnostic data for use in facilitating ophthalmic disease research through the NEI clinical service. Individuals have been recruited into multiple studies within the NEI clinical program, including NCT02077894, NCT01432847, NCT00378742, and NCT02471287. Diagnostic testing is sent through commercial laboratories. Specific tests are performed in-house via CLIA-certified genetic testing, including X-linked retinoschisis, blue cone monochromacy, and site-directed testing for familial segregation and research finding confirmation. Clinical reports are returned to clinic, and clinical phenotyping and molecular diagnostic results are directly compared and discussed in regular clinical molecular rounds meetings. For biospecimen management, over DNA samples from over 4000 patients and more than 30 patient cell lines are maintained within the laboratory. Represented heritable ocular conditions include but are not limited to: Achromatopsia, Albinism, Aniridia, Coloboma, Microphthalmia, Anophthalmia, Axenfeld-Rieger Syndrome, Best Disease, Bietti's Crystalline Dystrophy, Choroideremia, Cone Rod Dystrophy, Congenital Stationary Night Blindness, Corneal Dystrophy, Juvenile X-linked Retinoschisis, Leber Hereditary Optic Neuropathy (LHON), mitochondrial DNA disorders, Optic Atrophy Type 1, Pattern Dystrophy, Retinitis Pigmentosa, Sorsby Fundus Dystrophy, Stickler Syndrome and Stargardt Disease, and Usher Syndrome. The laboratory has also developed a bioinformatics pipeline for processing next-generation sequencing data, including panel, exome, and genome datasets, for annotating different variation types such as single nucleotide variants, insertions-deletions, large deletions, and duplications, and structural variations including translocations. Variant prioritization tools are developed by the lab using large disease cohorts, internal variant frequencies, and development of pipeline annotations such as variation constraint, in silico predictors, and published epigenomic datasets. As such, the Ophthalmic Genomics Laboratory is a fully integrated, clinical functional genomic laboratory supporting NEI clinical care, research efforts, and extramural collaborations.