شناسایی جهش PSEN1 p.M233L و p.R352C در خانواده هان چینی با بیماری زودرس آلزایمر خانوادگی

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.

Early-onset familial Alzheimer's disease (EOFAD) is characterized by the onset of progressive dementia symptoms before 65 years, positive family history, and more aggressive course than late-onset sporadic AD. To date, more than 230 mutations have been identified in the amyloid precursor protein (APP), the presenilin 1 (PSEN1), and the presenilin 2 (PSEN2) genes ( Bettens et al., 2010 and Wu et al., 2012). Hitherto, there are a few reports about the PSEN1, PSEN2, and APP gene mutations in Han Chinese families ( Jiao et al., 2014, Niu et al., 2014 and Peng et al., 2014). Further mutation profiling is needed. In this study, we screened mutations of the 3 AD causal genes in 4 Han Chinese EOAD families. Two PSEN1 mutations (p.M233L and p.R352C) were identified in 2 of the 4 EOAD families. According to searches with available genetic database, p.R352C is a previously unidentified PSEN1 mutation, and p.M233L has been reported in European patients. The 2 mutations are associated with cognitive impairment and quite different clinical spectrum.