title: A novel presenilin 2 mutation (V393M) in early-onset dementia with profound language impairment.
abstract: BACKGROUND
  Mutations in the Presenilin 2 gene (PSEN2) are rare causes of Alzheimer's disease (AD). Pathogenic mutations in the genes associated with autosomal dominant inherited AD have been shown to alter processing of the amyloid precursor protein (APP) resulting in a relative increase of the amount of Abeta42 peptide.
  
  
  RESULTS
  We present a patient with neuropathologically confirmed early-onset AD characterized by profound language impairment. The patient was heterozygous for a novel missense mutation in exon 11 of the PSEN2 gene leading to a predicted amino acid substitution from valine to methionine in position 393, a conserved residue. However, in vitro expression of PSEN2 V393M cDNA did not result in detectable increase of the secreted Abeta42/40 peptide ratio. The mutation was not found in 384 control individuals tested.
  
  
  CONCLUSIONS
  The possible pathogenic nature of the mutation is not clarified. We discuss the limitations of functional PSEN2 studies and the challenges associated with genetic counselling of family members at risk.
authors: Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. granhojlindquist@gmail.com
authors: S G
authors: SG
authors: Lindquist
authors: L
authors: L
authors: Hasholt
authors: J M C
authors: JM
authors: Bahl
authors: N H H
authors: NH
authors: Heegaard
authors: B B
authors: BB
authors: Andersen
authors: A
authors: A
authors: Nørremølle
authors: J
authors: J
authors: Stokholm
authors: M
authors: M
authors: Schwartz
authors: M
authors: M
authors: Batbayli
authors: H
authors: H
authors: Laursen
authors: R
authors: R
authors: Pardossi-Piquard
authors: F
authors: F
authors: Chen
authors: P
authors: P
authors: St George-Hyslop
authors: G
authors: G
authors: Waldemar
authors: J E
authors: JE
authors: Nielsen
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D019943:Amino Acid Substitution; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000473:pathology; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007806:Language Disorders / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008569:Memory Disorders / Q000453:epidemiology / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D009483:Neuropsychological Tests; D010375:Pedigree; D010446:Peptide Fragments / Q000378:metabolism; D017354:Point Mutation; D053766:Presenilin-2 / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection
chemical_list: D016229:Amyloid beta-Peptides; D018076:DNA, Complementary; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053766:Presenilin-2; D011993:Recombinant Fusion Proteins; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)