PSEN1 M139L mutation in a Chinese pedigree with early‐onset familial Alzheimer's disease

Abstract

AbstractBackgroundpresenilin 1(PSEN1) is the most common gene associated with familial Alzheimer's disease. we reported a case with M139L mutation of PSEN1 which was reported as pathogenic mutation in February 2019.Methodchose an early‐onset Alzheimer's patient (proband) and her family (I‐V generation) as the research object. clinical and imaging data of the proband and her family members were collected. High throughput second generation exon sequencing and sanger method was used to analyze the gene of the proband.Result1. Proband clinical characteristic: The proband (IV8) started to progressive memory loss, especially short‐term memory at 38 years old. She can't work because of memory problem. Now she lives on her own, can use mobile phone and APP, drive, remember familiar roads, but cannot shop, take bus to new place, handle own finances. The MMSE score was 27/30, and the MOCA score was 20/30 (delayed recall, time orientation, visuospatial disfunction, calculation) (Figure 1). Brain Magnetic Resonance Imaging suggested hippocampal atrophy (Figure 2). 2. Family phenotypic distribution (Figure 3): The onset age of Alzheimer's disease in this family was early, starting between 38 and 55 years old. The first and prominent clinical manifestations were memory loss, followed by orientation and executive function impairment. Movement disorder appears later or does not appear. It may have mild anxiety or depression. 3. Gene results (Figure 4): a heterozygotic mutation was found in the exon region of the PSEN1 gene: c.415A>T (adenine > thymine), resulting in an amino acid change of p.139l (methionine > leucine).ConclusionWe reported the early onset familial Alzheimer's disease caused by M139L mutation of PSEN1 in Han Chinese family which was helpful to enrich the clinical phenotypic characteristics of early onset familial Alzheimer's disease associated with PSEN1 mutation.