Reznik-Wolf H, Treves T A, Shabtai H, Aharon-Peretz J, Chapman J, Davidson M, Barkai G, Hyslop P H, Goldman B, Korczyn A D, Friedman E
Institute of Genetics, Elias Sourasky Medical Center, Tel-Aviv, Israel.
Eur J Hum Genet. 1998 Mar-Apr;6(2):176-80. doi: 10.1038/sj.ejhg.5200160.
Germ line mutations in three genes have been detected in patients with familial Alzheimer's disease (FAD) and sporadic, early onset disease: amyloid precursor protein (APP), presenilin 1 (PS-1), and presenilin 2 (PS-2). The relative proportions in which mutations in these genes occur among AD patients in Israel has not been evaluated. To that end, we screened 52 Jewish-Israeli patients with AD: 22 with sporadic, early-onset disease (below 65 years), and 30 with FAD. Mutation screen employed denaturing gradient gel electrophoresis (DGGE) of exon-specific PCRs and restriction enzyme digest. Five patients from three different families displayed mutations within the PS-1 gene: three patients of one family showed a mis-sense mutation in codon 120 (Glu 120Lys), and two other unrelated patients showed an identical mis-sense mutation in codon 318 (Glu318Gly). No patient showed an abnormal migration on DGGE (for APP) or mutant restriction digest pattern (for PS-2) genes. These data may indicate the existence of another familial Alzheimer disease (FAD) gene locus in the Israeli Jewish population.
在患有家族性阿尔茨海默病（FAD）以及散发性早发型疾病的患者中，已检测到三个基因的种系突变：淀粉样前体蛋白（APP）、早老素1（PS-1）和早老素2（PS-2）。这些基因的突变在以色列AD患者中出现的相对比例尚未评估。为此，我们对52名以色列犹太裔AD患者进行了筛查：22名患有散发性早发型疾病（65岁以下），30名患有FAD。突变筛查采用外显子特异性PCR的变性梯度凝胶电泳（DGGE）和限制性酶切。来自三个不同家族的五名患者在PS-1基因内显示出突变：一个家族的三名患者在密码子120处出现错义突变（Glu 120Lys），另外两名无亲缘关系的患者在密码子318处出现相同的错义突变（Glu318Gly）。没有患者在DGGE（针对APP）或突变限制性酶切模式（针对PS-2）基因上显示出异常迁移。这些数据可能表明在以色列犹太人群体中存在另一个家族性阿尔茨海默病（FAD）基因位点。
