Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland |
| |
Authors: | 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 |
| |
Institution: | Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland. czarekz@iimcb.gov.pl |
| |
Abstract: | 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. |
| |
Keywords: | Early-onset Alzheimer's disease Familial Alzheimer's disease Mutation PSEN1 PSEN2 APP Polymorphism |
本文献已被 ScienceDirect PubMed 等数据库收录! |