title: A Polish pedigree with Alzheimer's disease determined by a novel mutation in exon 12 of the presenilin 1 gene: clinical and molecular characterization.
abstract: The presenilin 1 (PS-1) gene, recently identified on chromosome 14q24.3, is a major gene involved into the autosomal dominant forms of early onset Alzheimer's disease (EOAD). Mutations of the PS-1 gene are responsible for the majority of familial EOAD. We found a novel mutation in a Polish family with EOAD from the Poznań region. The mutation at codon 424 in exon 12 of the PS-1 gene leads to an amino acid substitution Leu-Arg in a transmembrane domain VIII of the presenilin 1 molecule. The change is predicted to have a drastic effect on the protein function because it is associated with a very early age of onset (a range of 30-35 years) and a quick progression (about a 4-5 years duration) of the disease.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznań.
authors.forename: A
authors.initials: A
authors.lastname: Kowalska
authors.forename: C
authors.initials: C
authors.lastname: Forsell
authors.forename: J
authors.initials: J
authors.lastname: Florczak
authors.forename: D
authors.initials: D
authors.lastname: Pruchnik-Wolińska
authors.forename: R
authors.initials: R
authors.lastname: Modestowicz
authors.forename: W
authors.initials: W
authors.lastname: Paprzycki
authors.forename: M
authors.initials: M
authors.lastname: Wender
authors.forename: L
authors.initials: L
authors.lastname: Lannfelt
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics*; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology; D003062:Codon / Q000235:genetics; D018450:Disease Progression; D005091:Exons / Q000235:genetics*; D005260:Female; D005796:Genes / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D011044:Poland; D014057:Tomography, X-Ray Computed
chemical_list: D003062:Codon