title: Mutation screening of patients with Alzheimer disease identifies APP locus duplication in a Swedish patient.
abstract: BACKGROUND
  Missense mutations in three different genes encoding amyloid-β precursor protein, presenilin 1 and presenilin 2 are recognized to cause familial early-onset Alzheimer disease. Also duplications of the amyloid precursor protein gene have been shown to cause the disease. At the Dept. of Geriatric Medicine, Karolinska University Hospital, Sweden, patients are referred for mutation screening for the identification of nucleotide variations and for determining copy-number of the APP locus.
  
  
  METHODS
  We combined the method of microsatellite marker genotyping with a quantitative real-time PCR analysis to detect duplications in patients with Alzheimer disease.
  
  
  RESULTS
  In 22 DNA samples from individuals diagnosed with clinical Alzheimer disease, we identified one patient carrying a duplication on chromosome 21 which included the APP locus. Further mapping of the chromosomal region by array-comparative genome hybridization showed that the duplication spanned a maximal region of 1.09 Mb.
  
  
  CONCLUSIONS
  This is the first report of an APP duplication in a Swedish Alzheimer patient and describes the use of quantitative real-time PCR as a tool for determining copy-number of the APP locus.
authors: Genetics Unit, Dept of Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden. hakan.thonberg@karolinska.se.
authors: Håkan
authors: H
authors: Thonberg
authors: Marie
authors: M
authors: Fallström
authors: Jenny
authors: J
authors: Björkström
authors: Jacqueline
authors: J
authors: Schoumans
authors: Inger
authors: I
authors: Nennesmo
authors: Caroline
authors: C
authors: Graff