Early⁃onset Alzheimer's disease caused by PSEN1 gene mutation: two cases reports and literature review

Abstract

Objective To report 2 pedigrees of early⁃onset familial Alzheimer's disease (EOFAD) caused by PSEN1 gene mutation, review previous studies and summarize the PSEN1 gene mutation sites, clinical presentation and genotype characteristics of EOFAD in China. Methods and Results The clinical data of 2 pedigrees with EOFAD from Beijing Tiantan Hospital, Capital Medical University were collected. Genomic DNA from peripheral venous blood of the proband was screened. Search the reported Chinese cases of EOFAD caused by PSEN1 gene mutation. In the Case 1 family, there were 3 members with memory loss, including the proband, onset at the age of 45. His head MRI showed mild atrophy of the cerebral cortex and bilateral hippocampus. A c.488A＞G (p.His163Arg) pathogenic mutation in the exon 6 of PSEN1 gene was found, proving the diagnosis. In the Case 2 family, there were 6 members with memory and working competence loss, including the proband, onset at the age of 42. Head MRI showed whole cerebral cortical atrophy and bilateral hippocampal atrophy, obviously on the left side. A c.344A＞G (p.Tyr115Cys) pathogenic mutation in the exon 5 of PSEN1 gene was found, proving the diagnosis. A total of 40 cases (including this 2 cases) of EOFAD patients caused by PSEN1 gene mutation in China were enrolled. Thirty⁃eight pathogenic mutation sites were reported. The age of onset ranged from 21 to 62 years old, and the course of disease ranged from 4 to 10 years. About 87.50% (35/40) of the patients' onset manifestation was progressive memory loss and then rapidly with multiple cognitive domains involved. Some patients manifested with extrapyramidal symptoms, epilepsy or ear symptoms. Conclusions c.488A＞G and c.344A＞G mutations in the PSEN1 gene were identified to cause EOFAD, and c.344A＞G mutation is the first report in China. EOFAD occurs early and progresses rapidly, and sometimes the initial symptoms may be atypical. Therefore, gene detection plays an important role in the diagnosis of the disease.

doi：10.3969/j.issn.1672⁃6731.2021.11.008