The authors review the utility of genetic testing in ophthalmic disorders – precise diagnosis, accurate prognosis, genetic counseling, prenatal diagnosis, and entry into gene-specific therapeutic trials. The prerequisites for a successful outcome of a genetic test are an accurate clinical diagnosis, a careful family history that guides which genes to study, and genetic counseling (both pre-test and post-test). The common eye disorders for which genetic testing is commonly requested are briefly discussed – anophthalmia, microphthalmia, coloboma, anterior segment dysgenesis, corneal dystrophies, cataracts, optic atrophy, congenital glaucoma, congenital amaurosis, retinitis pigmentosa, color blindness, juvenile retinoshisis, retinoblastoma etc. A protocol for genetic testing is presented. If specific mutations in a gene are common, they should form the first tier test, as the mutations in Leber hereditary optic neuropathy. If mutations in one gene are likely, sequencing of that gene should be carried out, e.g. GALT gene in galactosemia, RS1 gene in retinoshisis. Disorders with genetic heterogeneity require multi-gene panel tests, and if these show no abnormality, then deletion / duplication or microarray studies are recommended, followed in sequence by clinical exome (5000 to 6000 genes), full exome (about 20,000 genes or whole genome studies (includes all introns). It is fortunate that most genetic tests in ophthalmology are available in India, including gene panel and whole exome/genome sequencing tests.
Moore T, Burton H. A needs assessment and review of specialist services for genetic eye disorders. Report for the United Kingdom Genetic Testing Netwrok. PHG Foundation. 2008. Available at: http://www.phgfoundation.org/. Accessed 15 July 2017.
Musleh M, Hall G, Lloyd IC, et al. Diagnosing the cause of bilateral paediatric cataracts: comparison of standard testing with a next-generation sequencing approach. Eye (Lond). 2016;30:1175–81.CrossRefGoogle Scholar
Tanwar M, Dada T, Sihota R, Das TK, Yadav U, Dada R. Mutation spectrum of CYP1B1 in north Indian congenital glaucoma patients. Mol Vis. 2009;15:1200–9.PubMedPubMedCentralGoogle Scholar
Paliwal P, Sharma A, Tandon R, et al. Congenital hereditary endothelial dystrophy - mutation analysis of SLC4A11 and genotype-phenotype correlation in a north Indian patient cohort. Mol Vis. 2010;16:2955–63.PubMedPubMedCentralGoogle Scholar
Li WL, Buckley J, Sanchez-Lara PA, et al. Rapid and sensitive next-generation sequencing method to detect RB1 mutations improves care for retinoblastoma patients and their families. J Mol Diagn. 2016;18:480–93.CrossRefPubMedGoogle Scholar
Verma IC, Bijarnia S, Saxena R, et al. Leber's hereditary optic neuropathy with molecular characterization in two Indian families. Indian J Ophthalmol. 2005;53:167–71.CrossRefPubMedGoogle Scholar
Kumaramanickavel G, Joseph B, Vidhya A, Arokiasamy T, Shridhara SN. Consanguinity and ocular genetic diseases in South India: analysis of a five-year study. Community Genet. 2002;5:182–5.CrossRefPubMedGoogle Scholar
Sen P, Bhargava A, George R, et al. Prevalence of retinitis pigmentosa in south Indian population aged above 40 years. Ophthalmic Epidemiol. 2008;15:279–81.CrossRefPubMedGoogle Scholar
Yang Y, Yang Y, Huang L, et al. Whole exome sequencing identified novel CRB1 mutations in Chinese and Indian populations with autosomal recessive retinitis pigmentosa. Sci Rep. 2016;6:33681.CrossRefPubMedPubMedCentralGoogle Scholar
Stone EM, Aldave AJ, Drack AV, et al. Recommendations for genetic testing of inherited eye diseases: report of the American Academy of ophthalmology task force on genetic testing. Ophthalmology. 2012;119:2408–10.CrossRefPubMedGoogle Scholar