title: Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer's disease in Poland.
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.
authors.affiliation: Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland. czarekz@iimcb.gov.pl
authors.forename: Cezary
authors.initials: C
authors.lastname: Zekanowski
authors.forename: Maria
authors.initials: M
authors.lastname: Styczyńska
authors.forename: Beata
authors.initials: B
authors.lastname: Pepłońska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gabryelewicz
authors.forename: Dorota
authors.initials: D
authors.lastname: Religa
authors.forename: Jan
authors.initials: J
authors.lastname: Ilkowski
authors.forename: Beata
authors.initials: B
authors.lastname: Kijanowska-Haładyna
authors.forename: Sławomira
authors.initials: S
authors.lastname: Kotapka-Minc
authors.forename: Sanne
authors.initials: S
authors.lastname: Mikkelsen
authors.forename: Anna
authors.initials: A
authors.lastname: Pfeffer
authors.forename: Anna
authors.initials: A
authors.lastname: Barczak
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Łuczywek
authors.forename: Bogusław
authors.initials: B
authors.lastname: Wasiak
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Chodakowska-Zebrowska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gustaw
authors.forename: Jarosław
authors.initials: J
authors.lastname: Łaczkowski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sobów
authors.forename: Jacek
authors.initials: J
authors.lastname: Kuźnicki
authors.forename: Maria
authors.initials: M
authors.lastname: Barcikowska
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008403:Mass Screening; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011044:Poland / Q000453:epidemiology; D018807:Polymorphism, Single-Stranded Conformational; D053764:Presenilin-1; D053766:Presenilin-2
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2