title: Novel presenilin-1 Y159F sequence variant associated with early-onset Alzheimer's disease.
abstract: BACKGROUND
  Mutations in the gene for presenilin-1 cause familial, early-onset Alzheimer's disease.
  
  
  METHODS
  We report the case of a 43-year-old woman presenting with progressive cognitive decline and a family history of early-onset dementia. Her workup included cerebrospinal fluid amyloid-beta, tau, and phospho-tau levels, as well as genetic sequencing of genes implicated in familial Alzheimer's disease.
  
  
  RESULTS
  Cerebrospinal fluid biomarkers were consistent with a diagnosis of Alzheimer's disease. A novel nucleotide sequence variant (A476T) was discovered in one allele for presenilin-1, corresponding to a missense tyrosine-to-phenylalanine change at codon 159 (Y159F). An affected maternal uncle carried the same allele. The sequence variant occurs in a conserved region of the gene near other previously reported mutations.
  
  
  CONCLUSIONS
  This novel presenilin-1 sequence variant cosegregated with early onset dementia in the proband and at least one other affected family member, and likely represents a mutation causing familial, early-onset Alzheimer's disease.
authors.affiliation: Stanford Center for Memory Disorders and Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. kerchner@stanford.edu
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Kerchner
authors.forename: Karen
authors.initials: K
authors.lastname: Holbrook
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000235:genetics*; D000595:Amino Acid Sequence; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D053764:Presenilin-1 / Q000235:genetics*
chemical_list: C508853:PSEN1 protein, human; D053764:Presenilin-1