Segregation of a rare TTC3 variant in an extended family with late-onset Alzheimer disease.

ABSTRACT:

Objective

The genetic risk architecture of Alzheimer disease (AD) is complex with single pathogenic mutations leading to early-onset AD, while both rare and common genetic susceptibility variants contribute to the more widespread late-onset AD (LOAD); we sought to discover novel genes contributing to LOAD risk.

Methods

Whole-exome sequencing and genome-wide genotyping were performed on 11 affected individuals in an extended family with an apparent autosomal dominant pattern of LOAD. Variants of interest were then evaluated in a large cohort of LOAD cases and aged controls.

Results

We detected a single rare, nonsynonymous variant shared in all 11 LOAD individuals, a missense change in the tetratricopeptide repeat domain 3 (TTC3) gene. The missense variant, rs377155188

SUBMITTER: Kohli MA 

PROVIDER: S-EPMC4817909 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature