Genetic characterization of Stargardt clinical phenotype in South Indian patients using sanger and targeted sequencing

Background:Stargardt disease 1(STGD1;MIM 248200)is a monogenic form of autosomal recessive genetic disease caused by mutation in ABCA4.This gene has a major role in hydrolyzing N-retinylidene-phosphatidylethanolamine to all-trans-retinal and phosphatidylethanolamine.The purpose of this study is to identify the frequency of putative disease-causing mutations associated with Stargardt disease in a South Indian population.Methods:A total of 28 clinically diagnosed Stargardt-like phenotype patients were recruited from south India.Ophthalmic examination of all patients was carefully carried out by a retina specialist based on the stages of fundus imaging and ERG grouping.Genetic analysis of ABCA4 was performed for all patients using Sanger sequencing and clinical exome sequencing.Results:This study identified disease-causing mutations in ABCA4 in 75%(21/28)of patients,7%(2/28)exhibited benign variants and 18%(5/28)were negative for the disease-causing mutation.Conclusion:This is the first study describing the genetic association of ABCA4 disease-causing mutation in South Indian Stargardt 1 patients(STGD1).Our findings highlighted the presence of two novel missense mutations and an(in/del,single base pair deletion&splice variant)in ABCA4.However,genetic heterogeneity in ABCA4 mutants requires a larger sample size to establish a true correlation with clinical phenotype.