A pedigree study on early ⁃ onset Alzheimer's disease associated with PSEN2 V214L mutation

Abstract

Objective To report clinical phenotype and gene mutation characteristics of one case of early⁃onset Alzheimer's disease (EOAD) associated with PSEN2 V214L mutation and conduct a pedigree analysis. Methods and Results A 63⁃year⁃old male proband with no family history of dementia, onset at 58 years old, had memory loss as the first manifestation and progressive aggravation of symptoms. Neuropsychological tests showed a score of 1 on Mini⁃Mental State Examination (MMSE), 0 on Montreal Cognitive Assessment (MoCA), 71 on Activities of Daily Living Scale (ADL), and 3 on Hachinski Ischemic Score (HIS). Head MRI revealed extensive cortical atrophy, with prominent atrophy of bilateral hippocampal, multiple hyperintensity in deep white matter (Fazekas grade 2). Exons of high⁃throughput sequencing of dementia⁃related genes showed that both the proband and his sister had heterozygous missense mutations in exon 8 of PSEN2 gene c.640G>T (p.V214L) and heterozygous splicing mutations in exon 28 of SORL1 gene c.3815⁃4A>C. The proband was finally diagnosed with EOAD associated with PSEN2 V214L mutation, and the proband's sister was considered as an absolute risk group for Alzheimer's disease (AD). Conclusions The PSEN2 V214L mutation probably causes EOAD. Further investigations should be conducted to evaluate the effects on the production of amyloid β⁃protein 40 and 42 (Aβ₄₀ and Aβ₄₂), then verify its pathogenicity.

doi：10.3969/j.issn.1672⁃6731.2023.04.010