title: Nonsense mutation in PRNP associated with clinical Alzheimer's disease.
abstract: Here, we describe a nonsense haplotype in PRNP associated with clinical Alzheimer's disease. The patient presented an early-onset of cognitive decline with memory loss as the primary cognitive problem. Whole-exome sequencing revealed a nonsense mutation in PRNP (NM_000311, c.C478T; p.Q160*; rs80356711) associated with homozygosity for the V allele at position 129 of the protein, further highlighting how very similar genotypes in PRNP result in strikingly different phenotypes.
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, England.
authors: Rita
authors: R
authors: Guerreiro
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, England.
authors: José
authors: J
authors: Brás
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors: Aleksandra
authors: A
authors: Wojtas
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors: Rosa
authors: R
authors: Rademakers
authors: Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, England. Electronic address: j.hardy@ucl.ac.uk.
authors: John
authors: J
authors: Hardy
authors: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA; Department of Neurology, Mayo Clinic, Jacksonville, FL, USA.
authors: Neill
authors: N
authors: Graff-Radford
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics; D059472:Exome / Q000235:genetics; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008569:Memory Disorders / Q000235:genetics; D010641:Phenotype; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics*; D017421:Sequence Analysis
chemical_list: D018389:Codon, Nonsense; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions
keywords: Alzheimer's disease; Exome sequencing; Nonsense mutation; PRNP; Prion