Kamimura K, Tanahashi H, Yamanaka H, Takahashi K, Asada T, Tabira T
Department of Demyelinating Disease and Aging, NCNP, Kodaira, Tokyo, Japan.
J Neurol Sci. 1998 Sep 18;160(1):76-81. doi: 10.1016/s0022-510x(98)00219-6.
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 epsilon4, important FAD genes or risk-factor genes remain to be identified.
早发性家族性阿尔茨海默病（FAD）与早老素1（PS - 1）基因中的40多个错义突变和1个剪接位点突变、早老素2（PS - 2）的2个错义突变以及淀粉样前体蛋白（APP）的3个以上错义突变共分离。为了确定这些基因的突变在日本患者中的发生率，我们使用单链构象多态性（SSCP）分析，对25个早发性FAD家系、1例晚发性FAD病例、33例早发性AD病例和5例晚发性AD病例的基因编码区突变进行了筛查。在5个早发性FAD家系中鉴定出4种不同的PS - 1基因错义突变，包括一种新突变Glu273Ala，在1例散发性AD患者中鉴定出1种PS - 1错义突变。虽然未检测到PS - 2的错义突变，但观察到4种沉默核苷酸替代。我们的数据表明，在日本，PS - 1突变占早发性FAD病例的20.0%。由于在其余病例中未发现PS - 2和APP基因的突变，而这仅部分地可由载脂蛋白Eε4解释，因此仍有待鉴定重要的FAD基因或风险因素基因。
