TY - JOUR T1 - Mutation burden profile in familial Alzheimer's disease cases from India. JF - Neurobiol Aging Y1 - 2018 A1 - Syama, Adhikarla A1 - Sen, Somdatta A1 - Kota, Lakshmi Narayanan A1 - Viswanath, Biju A1 - Purushottam, Meera A1 - Varghese, Mathew A1 - Jain, Sanjeev A1 - Panicker, Mitradas M A1 - Mukherjee, Odity KW - Aged KW - Alzheimer Disease KW - Amyloid beta-Protein Precursor KW - Genetic Association Studies KW - Genetic Predisposition to Disease KW - Genetic Variation KW - Humans KW - India KW - LDL-Receptor Related Proteins KW - Membrane Transport Proteins KW - Middle Aged KW - Mutation KW - Presenilin-1 KW - Risk KW - Signal Transduction KW - Tissue Plasminogen Activator KW - Whole Exome Sequencing AB -

This study attempts to identify coding risk variants in genes previously implicated in Alzheimer's disease (AD) pathways, through whole-exome sequencing of subjects (N = 17) with AD, with a positive family history of dementia (familial AD). We attempted to evaluate the mutation burden in genes encoding amyloid precursor protein metabolism and previously linked to risk of dementias. Novel variants were identified in genes involved in amyloid precursor protein metabolism such as PSEN1 (chr 14:73653575, W161C, tgg > tgT), PLAT (chr 8:42039530,G272R), and SORL1 (chr11:121414373,G601D). The mutation burden assessment of dementia-related genes for all 17 cases revealed 45 variants, which were either shared across subjects, or were present in just the 1 patient. The study shows that the clinical characteristics, and genetic correlates, obtained in this sample are broadly comparable to the other studies that have investigated familial forms of AD. Our study identifies rare deleterious genetic variations, in the coding region of genes involved in amyloid signaling, and other dementia-associated pathways.

VL - 64 ER -