Genetic testing for inherited ocular conditions in a developing country

Mario Zanolliab*, Joaquín I. Oportoc , Juan I. Verdaguerd, Juan Pablo Lópeza, Sergio Zacharíasd, Pablo Romeroa, Diego Ossandónab, Oliver Denka, Olga Acuñad, José Manuel Lópezd, Ricardo Stevensone, Bernardita Álamosf & Hernán Iturriagada Clínica Alemana de Santiago- Facultad de Medicina, Universidad del Desarrollo, Santiago, Chileb Departamento de oftalmología, Hospital de niños Roberto del Río, Santiago, Chilec Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chiled Fundación Oftalmológica Los Andes, Universidad de los Andes, Santiago, Chilee Centro de la Visión, Santiago, Chilef Instituto Oftalmológico Integral, Santiago, ChileCONTACT Mario Zanolli mario.zanolli@me.com Facultad de Medicina Universidad del Desarrollo, Clínica Alemana de Santiago, Santiago, ChileABSTRACTBackground: Inherited ocular conditions are a frequent cause of blindness. Gene therapy has encouraged the development of genetic testing, currently able to detect up to 80% of mutations in contrast to the 5% sensitivity achieved a few decades ago.Materials and methods: One hundred sixty-three patients with suspected genetic ocular disorders who were referred to a single clinician between August 2014 and August 2019 underwent a thorough ophthalmologic examination. Those diagnosed with congenital cataract, retinoblastoma, anterior segment dysgenesis, autoimmune retinal disease, posterior microphthalmia, or cobalamin C deficiency were excluded, along with patients who opted against genetic testing. Included probands were classified into a diagnostic clinical category and offered genetic testing. Blood samples were sent to foreign accredited diagnostic laboratories, followed by clinical interpretation of the results.Results: Of the 163 patients referred, 104 were enrolled in the study. Median age at disease onset was 2 years (range, 0 to 43 years). A molecular diagnosis was established at a median age of 10 years (range, 0.4 to 50 years). Disease-causing genotypes were identified in 82 of the probands, indicating a mutation detection rate of 78.8%. Mutations were identified in 38 genes, ABCA4 being the most commonly affected (23% of mutations), followed by CRB1 (13% of mutations). Whole-exome sequencing was performed in 6 patients, resulting in a definite diagnosis in 3 (50%).Conclusions: Molecular testing for inherited ocular conditions is feasible in developing countries by sending samples to certified foreign laboratories, with a mutation detection rate comparable to published values in developed countries. Further studies to identify more disease-causing genes may improve the overall sensitivity.