1. Genetic tests: DDL currently offers Sanger sequencing tests in 8 clinical diagnostic categories involving 12 genes (Table 1). Table 1. Current Clinical Genetic Testing Protocols in the DDL Genetic Testing Operation Diseases Gene Method 1 X-linked Retinoschisis RS1 CDS Sanger sequencing 2 Bietti Cryslline Corneoretinal Dystrophy CYP4V2 CDS Sanger sequencing 3 X-linked Congenital Stationary Night blindness NYX CDS Sanger sequencing 4 Oculacutenous Albinism type 1 TYR CDS Sanger sequencing 5 Oculacutenous Albinism type 2 OCA2 CDS Sanger sequencing 6 Cone Rod Dystrophy GUCY2D Target mutation by sequencing 7 Occult Macular Dystrophy RP1L1 Target mutation by sequencing 8 Achromatopsia CNGA3 CDS Sanger sequencing 9 Achromatopsia CNGB3 CDS Sanger sequencing 10 Corneal Dystrophy, lattice type TGFBI CDS Sanger sequencing 11 Meesmann Corneal Dystrophies KRT3 CDS Sanger sequencing 12 Meesmann Corneal Dystrophies KRT12 CDS Sanger sequencing 2. Compliance with CLIA regulations Since 2009, DDL has established a standard annual review of protocols to comply with CLIA regulations. An increasing numbers of clinical protocols have been implemented in the DDL since 2009. DDL also commits to continued quality improvement (CQI) by applying new methods, new procedures, and modified criteria/protocols in a compliance with current QA protocols. Implementation of CQIs have resulted in improved accuracy of tests, faster turnaround time and reduced operating costs. Regular maintenance of equipment, including pipettes, thermocyclers and sequencers, is also required to ensure continued accuracy of clinical testing. 3. Reporting of testing results The DDL genetic testing operation has delivered 103 reports back to clinicians (including the eyeGENE Coordinating Center) in the 2013 budget year (Table 2). The majority of them were in support of clinical trials, patient care, clinical research and the eyeGENE operation. Table 2. Summary of Clinical Reports from DDL Genetic Testing Operation Gene Methods Reports RS1 CDS Sanger sequencing 19 CYP4V2 CDS Sanger sequencing 5 NYX CDS Sanger sequencing 2 TYR CDS Sanger sequencing 22 OCA2 CDS Sanger sequencing 6 GUCY2D Target mutation by sequencing 10 CNGA3 CDS Sanger sequencing 6 CNGB3 CDS Sanger sequencing 6 TGFBI CDS Sanger sequencing 15 RP1L1 Target mutation by sequencing 12 4. Continuing the development of new tests/protocols for clinical services DDL is committed to developing additional clinical tests to further support NEI intramural clinical patient care and clinical research, extramural and eyeGENE program. DDL has been focusing on potential tests that are not clinically available in the community and/or engaging in advanced technology or methodology that are not commonly accessible or reimbursable in the standard care of patients. We have technically developed and are performing the following Sanger sequencing assays for research purposes: a. GPR143 gene CDS sequencing for Ocular Albinism b. PAX2 gene CDS sequencing for Papillorenal Syndrome c. RP1L1 gene CDS sequencing for Occult Macular Dystrophy (OMD) d. Collaborations in new test development: During the development of several new tests, the DDL did not have sufficient control samples for evaluation and validation. DDL collaborated with intramural and extramural communities for the development of new clinical genetic tests. Dr. James Fielding Hejtmancik from the OGVFB provided 2 mutation positive samples to make it possible for the revalidation of the NYX gene sequencing assay. Dr. Anthony Aldave from UCLA provided 3 mutation positive samples for the validation of KRT3/KRT12 gene sequencing assays. NEI Board of Scientific Counselors Review: The NEI DNA Diagnostic Laboratory had its BSC review in April 2014. DDL operations are being reorganized based on the recommendations from the BSC review. DDL will focus on the new tasks assigned to DDL.
| Simeonov, Dimitre R; Wang, Xinjing; Wang, Chen et al. (2013) DNA variations in oculocutaneous albinism: an updated mutation list and current outstanding issues in molecular diagnostics. Hum Mutat 34:827-35 |
| Sullivan, Lori S; Bowne, Sara J; Reeves, Melissa J et al. (2013) Prevalence of mutations in eyeGENE probands with a diagnosis of autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci 54:6255-61 |
| D'Souza, Leera; Cukras, Catherine; Antolik, Christian et al. (2013) Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis. Mol Vis 19:2209-16 |
| Wang, Xinjing; Cutting, Garry R (2011) Chronic rhinosinusitis. Adv Otorhinolaryngol 70:114-21 |
| Song, Jin; Smaoui, Nizar; Ayyagari, Radha et al. (2011) High-throughput retina-array for screening 93 genes involved in inherited retinal dystrophy. Invest Ophthalmol Vis Sci 52:9053-60 |
