Mutation Profile Of APP,PSEN1,PSEN2 In Chinese Familial Alzheimer’s Disease

Causative mutations in the genes encoding amyloid precursor protein(APP),presenilinl(PSEN1),or presenilini2(PSEN2)account for a majority of cases of familial Alzheimer’s disease(FAD)inherited as autosomal-dominant pattern.For the sake of characterized mutation,index patients from 148 families with FAD were enrolled from mainland China.Sanger sequencing of the genes APP(exon16-17),PSEN1(exon3-12)and PSEN2(exon4-7)was performed to characterize mutation spectrum in Chinese population.Additionally,parts of mutation proteins were analysed in silico analysis.One common pathogenic mutation(p.V717I)and a novel mutation(p.V695M)were found in APP(15.4%).Three novel missense mutations(P.V103G,p.M139L,p.F177V),five previously described mutations(p.F105V,p.L226F,p.L262F,p.L286V,p.I167del)of PSEN1(61.5%)and two novel PSEN2 mutations(p.V150M,p.R163C)(23.1%)were identified,respectively.PSEN1 mutations represent the largest proportions in familial AD,and PSEN2 mutations are responsible for late-onset familial AD in China.The analysis of genetic-clinical correlations concluded that the phenotypes are mainly influenced by specific genetic defects.