Hattori Sayoko, Sakuma Kenji, Wakutani Yosuke, Wada Kenji, Shimoda Masaru, Urakami Katsuya, Kowa Hisanori, Nakashima Kenji
Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, 36-1 Nishimachi, Yonago-shi 689-8504, Japan.
Neurosci Lett. 2004 Sep 30;368(3):319-22. doi: 10.1016/j.neulet.2004.07.057.
Early onset familial Alzheimer's disease with spastic paraparesis (FAD-SP) has been associated with mutations of the presenilin 1 gene (PSEN1). We report a pedigree of FAD-SP due to a novel missense mutation of PSEN1 (Y154N). The symptoms of the proband were characterized by presenile dementia in her 40s, preceded by spastic paraparesis in her 30s, whereas the mother of the proband presented with spastic paraparesis in her 40s, followed by symptoms of dementia in her mid 60s. The mutation was found only in the proband, and not in a normal family member, normal Japanese control subjects, patients with sporadic Alzheimer's disease or patients with familial spastic paraparesis without dementia. Thus, Y154N is a novel PSEN1 mutation responsible for FAD-SP of Japanese origin.
早发性家族性阿尔茨海默病伴痉挛性截瘫（FAD-SP）与早老素1基因（PSEN1）突变有关。我们报告了一个因PSEN1新的错义突变（Y154N）导致的FAD-SP家系。先证者的症状表现为40多岁时出现早老性痴呆，在此之前30多岁时出现痉挛性截瘫，而先证者的母亲40多岁时出现痉挛性截瘫，60岁中期出现痴呆症状。该突变仅在先证者中发现，在正常家庭成员、正常日本对照受试者、散发性阿尔茨海默病患者或无痴呆的家族性痉挛性截瘫患者中均未发现。因此，Y154N是一种导致日本血统FAD-SP的新型PSEN1突变。
