Exome sequencing identifiesABCA7as an important gene for familial AD cases from Eastern India

Abstract

ABSTRACTIntroductionAD is the most complex disorder leading to dementia worldwide. Despite the disease burden among Indians the mutation spectrum in our subcontinent is not well examined.MethodsTo identify probable causal variants for AD, in a total of 29 clinically diagnosed, majorly familial and young onset AD cases from Eastern India, whole exome analysis in Illumina NovoSeq. 6000 sequencing platform was performed as per standard methodology. Next, the coding variants were prioritised based on the literature and our bioinformatic analyses for genotype-to-phenotype correlation.ResultsA total of 25 missense variants and 4 nonsense variants in 17 genes among 23 AD cases were identified as probable damaging ones in our study cohort. Amongst all,ABCA7account for the maximum number of pathogenic variants (5/29). A lowering in the age of onset was observed for mutation carriers and cases belonging to the posterior cortical atrophy (PCA) subgroup. Our further comparative analyses suggested that variants in APP metabolism pathway genes are more common in PCA, frontal AD, and young-onset multi-domain amnestic phenotypes than dysexecutive and typical AD.ConclusionOur study suggests that whole exome sequencing among Indian AD patients holds the potential to identify the most common gene as well as clinically relevant new causal variants which may highlight new insight into disease mechanism through future research.