疾病机理遗传学和进化医学学科组（姚永刚）知识库

Early-onset familial Alzheimer's disease (EOFAD) is characterized by the onset of dementia symptoms before 65 years, positive family history, high genetic predisposition, and an autosomal dominant inheritance. We aimed to investigate mutations and to characterize phenotypes in Chinese EOFAD families. Detailed clinical assessments and genetic screening for mutations in the presenilin 1 (PSEN1), presenilin 2, amyloid precursor protein, and APOE genes were carried out in 4 EOFAD families. Two PSEN1 mutations (p.R352C and p.M233L) were identified in 2 EOFAD families, respectively. Mutation p.M233L was associated with prominent very early onset, rapidly progressive dementia, and neurologic symptoms, whereas p.R352C was associated with a progressive dementia, psychiatric syndrome, and chronic disease course. Both mutations are predicted to be pathogenic. Our results showed that mutations in PSEN1 gene might be common in Chinese EOFAD families.