Gene mutation analysis of 3 families with early-onset Alzheimer's disease

Abstract

Objective To explore the clinical phenotypes and gene mutations of 3 patients with early onset Alzheimer′s disease (EOAD). Methods Three patients with EOAD who were diagnosed in the First Affiliated Hospital of Zhengzhou University were enrolled in the study. We extracted the genomic DNA from peripheral venous blood, and screened the common pathogenetic gene mutations of EOAD with polymerase chain reaction combined with Sanger sequencing, including presenilin 1 (PSEN1) gene, presenilin-2 (PSEN2) gene, the exons 16, 17 of amyloid precursor protein (APP) gene. Results The gene mutations of 3 cases all existed on the exon 7 of PSEN1. The first case was familial EOAD with PSEN1 gene mutation for two adjacent loci co-segregated in the family, while one was synonymous mutation and the other was novo mutation type Y256N. The second case was also familial EOAD with PSEN1 novo mutation type H214R. The third case was very early onset Alzheimer′s disease without family history and presented with a known mutation type G206V. Conclusions PSEN1 gene mutation is common in EOAD patients. In this study, two novo mutations and one known mutation of PSEN1 gene were certified, which enrich the known EOAD mutation types. Key words: Alzheimer disease; Presenilin 1; Gene mutation