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

摘要

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.