Familial cases presenting very early onset autosomal dominant Alzheimer’s disease with I143T in presenilin-1 gene: implication for genotype–phenotype correlation

Abstract

The amyloid precursor protein (APP), PS1, and PS2 genes have been identified as the causative genes for familial Alzheimer diseases (FAD). Given multiple causative genes, we are faced with the difficulty of providing a comprehensive mutational analysis for FAD. We have developed a microarray-based resequencing system and applied it to the mutational analysis of a Japanese family with unusually very early onset Alzheimer’s disease (AD). We designed microarrays (TKYAD01 and TKYPD01) [1]. TKYAD01 contains the APP, PS1, MAPT, CHT1, MME, PRNP, APOE, and BDNF genes. The PS2 gene is tiled onTKYPD01 to avoid cross hybridization with PS1. All the coding sequences and the splice sites were tiled on the microarrays. The sequences of interest were amplified using specific polymerase chain reaction primers (sequences are available as Electronic Supplementary Material 1) and subjected to hybridization to the microarray and sequence analysis according to the manufacturer’s instructions. Case 1 (III-4)