Rare Genetic Variant in SORL1 May Increase Penetrance of Alzheimer's Disease in a Family with Several Generations of APOE-ɛ4 Homozygosity.

ABSTRACT:

Background

The major genetic risk factor for late onset Alzheimer's disease (AD) is the APOE-ɛ4 allele. However, APOE-ɛ4 homozygosity is not fully penetrant, suggesting co-occurrence of additional genetic variants.

Objective

To identify genetic factors that, next to APOE-ɛ4 homozygosity, contribute to the development of AD.

Methods

We identified a family with nine AD patients spanning four generations, with an inheritance pattern suggestive of autosomal dominant AD, with no variants in PSEN1, PSEN2, or APP. We collected DNA from four affected and seven unaffected family members and performed exome sequencing on DNA from three affected and one unaffected family members.

Results

All affected family members were homozygous for the APOE-ɛ4 allele. Statistical analy

SUBMITTER: Louwersheimer E 

PROVIDER: S-EPMC5240543 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature