Abstract
More than 40 missense mutations and a splice-site mutation in the presenilin 1 (PS-1)
gene, two missense mutations of presenilin 2 (PS-2), and more than three missense
mutations of amyloid precursor protein (APP) cosegregate with early onset familial
Alzheimer's disease (FAD). In order to determine the incidence of mutations of these
genes in Japanese patients, we screened 25 early onset FAD families, one late-onset
FAD case, 33 early onset AD cases and five late-onset AD cases for mutations in the
coding regions of the genes using SSCP analysis. Four different missense mutations
of the PS-1 gene, including a novel mutation, Glu273Ala, were identified in five early
onset FAD families and one missense mutation of PS-1 in one isolated AD patient. While
no missense mutations of PS-2 were detected, four silent nucleotide substitutions
were observed. Our data indicate that PS-1 mutations account for 20.0% of early onset
FAD cases in Japan. Since mutations in PS-2 and APP genes were not found in the remaining
cases, which could be explained only partially by apolipoprotein E ε4, important FAD
genes or risk-factor genes remain to be identified.
Keywords
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Article info
Publication history
Accepted:
May 30,
1998
Received in revised form:
May 26,
1998
Received:
February 6,
1998
Identification
Copyright
© 1998 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
