title: Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients.
abstract: In order to assess the frequency of mutations in the known Alzheimer's disease causative genes in Turkish dementia patients we screened amyloid precursor protein (APP), PSEN1 and PSEN2 for mutations in a cohort of 98 Turkish dementia families. Six families were found to carry PSEN1 mutations (p.H163R, p.P264L, and p.H214Y) or variants suggested to cause the disease (p.L134R, p.L262V, and p.A396T). In 4 other families, previously reported PSEN2 variants were identified (p.R62H, p.R71W, p.M174V (n = 2), and p.S130L). The phenotype of the carriers varied from rapid progressing Alzheimer's disease to frontotemporal dementia, with spasticity and seizures also observed. Here we report a frequency of 11.2% of mutations and variants in the known Alzheimer disease genes in the dementia cohort studied and 24% in the early onset subgroup of patients, suggesting that mutations in these genes are not uncommon in Turkey and are associated with various phenotypes. We thus believe that genetic analysis should become a standardized diagnostic implement, not only for the identification of the genetic disease, but also for appropriate genetic counseling.
authors.affiliation: Department of Neurology, Faculty of Medicine, Istanbul University, Istanbul, Turkey. ebbalohmann@gmx.net
authors.forename: Ebba
authors.initials: E
authors.lastname: Lohmann
authors.forename: Rita J
authors.initials: RJ
authors.lastname: Guerreiro
authors.forename: Nihan
authors.initials: N
authors.lastname: Erginel-Unaltuna
authors.forename: Nicole
authors.initials: N
authors.lastname: Gurunlian
authors.forename: Basar
authors.initials: B
authors.lastname: Bilgic
authors.forename: Hakan
authors.initials: H
authors.lastname: Gurvit
authors.forename: Hasmet A
authors.initials: HA
authors.lastname: Hanagasi
authors.forename: Nga
authors.initials: N
authors.lastname: Luu
authors.forename: Murat
authors.initials: M
authors.lastname: Emre
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
mesh_terms: D000368:Aged; D003704:Dementia / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053764:Presenilin-1 / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors; D014421:Turkey / Q000453:epidemiology
chemical_list: D005819:Genetic Markers; C508853:PSEN1 protein, human; D053764:Presenilin-1