Zekanowski Cezary, Styczyńska Maria, Pepłońska Beata, Gabryelewicz Tomasz, Religa Dorota, Ilkowski Jan, Kijanowska-Haładyna Beata, Kotapka-Minc Sławomira, Mikkelsen Sanne, Pfeffer Anna, Barczak Anna, Łuczywek Elzbieta, Wasiak Bogusław, Chodakowska-Zebrowska Małgorzata, Gustaw Katarzyna, Łaczkowski Jarosław, Sobów Tomasz, Kuźnicki Jacek, Barcikowska Maria
Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
Exp Neurol. 2003 Dec;184(2):991-6. doi: 10.1016/S0014-4886(03)00384-4.
Mutations in three causative genes have been identified in patients with an autosomal-dominant form of early-onset Alzheimer's disease (EOAD). To determine the spectrum of mutations in a group consisting of 40 Polish patients with clinically diagnosed familial EOAD and 1 patient with mild cognitive impairment (MCI) and family history of AD, we performed a screening for mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2) and amyloid precursor protein (APP) genes. Four previously recognized pathogenic mutations in PSEN1 gene (H163R, M139V) and APP gene (T714A, V715A), and three novel putative mutations in PSEN1 gene (P117R and I213F) and PSEN2 gene (Q228L) were identified. The 34 patients with no mutations detected were older than the patients with mutations. A frequency of APOE4 allele was higher in this group. Frequency of mutations is relatively low (17%), possibly due to used operational definition of a patient with familial EOAD (a patient having at least one relative with early-onset dementia). It could be concluded that screening for mutations in the three genes could be included in a diagnostic program directed at patients with a positive family history or age of onset before 55 years.
在常染色体显性遗传形式的早发性阿尔茨海默病（EOAD）患者中，已鉴定出三个致病基因的突变。为了确定由40名临床诊断为家族性EOAD的波兰患者以及1名患有轻度认知障碍（MCI）且有阿尔茨海默病家族史的患者组成的群体中的突变谱，我们对早老素1（PSEN1）、早老素2（PSEN2）和淀粉样前体蛋白（APP）基因的突变进行了筛查。在PSEN1基因中鉴定出四个先前公认的致病突变（H163R、M139V）以及APP基因中的两个突变（T714A、V715A），并在PSEN1基因中鉴定出三个新的假定突变（P117R和I213F）以及PSEN2基因中的一个突变（Q228L）。未检测到突变的34名患者比有突变的患者年龄更大。该组中APOE4等位基因的频率更高。突变频率相对较低（17%），这可能是由于对家族性EOAD患者采用的操作定义（至少有一名亲属患有早发性痴呆的患者）所致。可以得出结论，对这三个基因的突变筛查可纳入针对有阳性家族史或发病年龄在55岁之前的患者的诊断程序中。
