title: A novel mutation in the predicted TM2 domain of the presenilin 2 gene in a Spanish patient with late-onset Alzheimer's disease.
abstract: Mutations in the presenilin-2 (PS-2) gene are less frequent than mutations in the PS-1 gene. All mutations described in the PS-1 gene were found in early-onset Alzheimer's disease (AD) patients. At present, there are two missense mutations described for the PS-2 gene in some AD pedigrees. We have therefore analyzed transmembrane 2 (TM2) and TM5 domains of the PS-2 gene in AD patients and in a group of age-matched healthy controls. In a patient who was clinically diagnosed as having late-onset AD, we found a novel missense mutation consisting of a G->A substitution on exon 5 of the PS-2 gene, which results in a Val to Ile substitution at codon 148 within the predicted TM2 domain of the PS-2 protein. This is the third mutation described in the PS-2 gene and the first presenilin mutation detected in a Spanish AD patient. Both, the N141I mutation and the V148I mutation described here are located within the predicted TM2 domain and both were found in late-onset AD kindreds, whereas the mutation within the predicted TM5 domain was found in an early-onset AD pedigree. Carriers of mutations within TM2 of PS-1 have a mean age at onset of 40 years, while the other mutations in PS-1 occur in families with a mean age at onset of 47 years. In summary, we report here the first mutation in a presenilin gene in a Spanish AD case, which is the third mutation detected for the PS-2 gene.
authors.affiliation: Department of Clinical and Molecular Genetics, Basic and Clinical Neurosciences Research Center, EuroEspes Biomedical Research Center, A Coruña, Spain.
authors.forename: J I
authors.initials: JI
authors.lastname: Lao
authors.forename: K
authors.initials: K
authors.lastname: Beyer
authors.forename: L
authors.initials: L
authors.lastname: Fernández-Novoa
authors.forename: R
authors.initials: R
authors.lastname: Cacabelos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D019943:Amino Acid Substitution; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000235:genetics; D005787:Gene Frequency; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D053764:Presenilin-1; D053766:Presenilin-2; D017434:Protein Structure, Tertiary / Q000235:genetics; D013030:Spain / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2