title: Atypical early-onset Alzheimer's disease caused by the Iranian APP mutation.
abstract: BACKGROUND
  Approximately 1% of all cases of Alzheimer's disease are inherited autosomal dominantly, and to date, three causative genes have been found, the Presenilin 1 (PSEN1) gene, the Presenilin 2 (PSEN2) gene and the Amyloid precursor protein (APP) gene. We describe atypical phenotypic features in a family with a pathogenic APP gene mutation and discuss possible explanations for these atypical features.
  
  
  RESULTS
  We report a family with a history of dementia compatible with autosomal dominant transmission. The disease course in the proband was not typical for Alzheimer's disease as the diagnosis was preceded by 8 years of an isolated amnesia. Further, the proband had epilepsy with complex partial seizures and central degenerative autonomic failure as determined by clinical physiology. Sequencing the three known causative Alzheimer genes revealed a pathogenic missense mutation, APP Thr714Ala (the Iranian mutation).
  
  
  CONCLUSIONS
  The atypical clinical phenotype with long prodromal phase, autonomic failure and seizures in this new proband with the APP Thr714Ala mutation illustrates the clinical heterogeneity in families with identical pathogenic mutations.
authors.affiliation: Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. suzanne.lindquist@rh.regionh.dk
authors.forename: Suzanne Granhøj
authors.initials: SG
authors.lastname: Lindquist
authors.forename: Jørgen Erik
authors.initials: JE
authors.lastname: Nielsen
authors.forename: Jette
authors.initials: J
authors.lastname: Stokholm
authors.forename: Marianne
authors.initials: M
authors.lastname: Schwartz
authors.forename: Mustafa
authors.initials: M
authors.lastname: Batbayli
authors.forename: Martin
authors.initials: M
authors.lastname: Ballegaard
authors.forename: Jesper
authors.initials: J
authors.lastname: Erdal
authors.forename: Katja
authors.initials: K
authors.lastname: Krabbe
authors.forename: Gunhild
authors.initials: G
authors.lastname: Waldemar
mesh_terms: D000409:Alanine / Q000235:genetics; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D001794:Blood Pressure; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D005192:Family Health; D006801:Humans; D007492:Iran / Q000208:ethnology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D013912:Threonine / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D013912:Threonine; D000409:Alanine