The authors analyzed 5 subjects and their families. Patient 1 was reported to have 2 disease-causing AIPL1 mutations. The family received incorrect prenatal counseling based on this result. The researchers found both variations to be benign ethnic polymorphisms. Case 2 had possible disease-causing mutations in RPE65, RPGRIP1, and CRB1; however, screening of family members revealed that only CRB1 variations were disease causing and the RPE65 change was a polymorphism found in 11% of African Americans. Case 3 had a diagnosis of CRB1-associated LCA, but this mutation was not disease causing; a true homozygous disease-causing mutation was later found in RDH12. Patient 4 had 3 mutations found in RPE65, but only 2 were disease causing. Patient 5 had a homozygous mutation in RPE65. Only Patients 4 and 5 would be eligible for clinical trials of RPE65 gene replacement, for which inclusion criteria are complex.

Writing in the article, Dr. Drack and colleagues state, "Gene therapy for patients with RPE65- associated LCA is now in clinical trials. Patients and families can be offered genetic testing, but results are complex and must be interpreted by practitioners with experience in both clinical and molecular genetics to avoid either ineffective treatment or lack of treatment due to an erroneous genetic diagnosis."

In an accompanying editorial, Elise H-on, MD, The Hospital for Sick Children, Toronto, comments on the complexity of the genetic screening needed to isolate patients who can benefit from the gene therapy. She writes, "Ocular gene therapy is not available for all retinal dystrophies - only RPE65-related LCA. -The article by Drack and colleagues nicely outlines how to screen for eligible patients and what to look for. This is timely and highlights important points relating this new era of ophthalmology: ocular gene therapy-The likely positive outcome of these trials highlights the critical contribution of the retinal clinician in identifying patients who can benefit from this remarkable therapy and in not misleading those who cannot."

Source: Elsevier Health Sciences