title: Clinical and pathological features of an Alzheimer's disease patient with the MAPT Delta K280 mutation.
abstract: We identified a case of Alzheimer's disease with a deletion of the lysine residue at codon 280 (DeltaK280) in exon 10-encoded microtubule-binding repeat domain of the tau gene (MAPT). This mutation was originally identified in a sporadic case of frontotemporal dementia (FTD) with a family history of Parkinson's disease. In the original report, the authors were careful in their assessment of the pathogenicity and suggested one could not be sure whether the mutation was pathogenic or not. The mutation has always presented a conundrum because it is the only known mutation, of assumed pathogenicity, which increases the proportion of 3-repeat tau mRNA in in vitro assays. Here we present the clinical and pathological features of a new case with this mutation and discuss whether the mutation is indeed pathogenic.
authors.affiliation: Laboratory of Neurogenetics, NIA, NIH Main Campus, Bethesda, MD 20892, USA.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Momeni
authors.forename: Alan
authors.initials: A
authors.lastname: Pittman
authors.forename: Tammaryn
authors.initials: T
authors.lastname: Lashley
authors.forename: Jana
authors.initials: J
authors.lastname: Vandrovcova
authors.forename: Elke
authors.initials: E
authors.lastname: Malzer
authors.forename: Connie
authors.initials: C
authors.lastname: Luk
authors.forename: Christine
authors.initials: C
authors.lastname: Hulette
authors.forename: Andrew
authors.initials: A
authors.lastname: Lees
authors.forename: Tamas
authors.initials: T
authors.lastname: Revesz
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Rohan
authors.initials: R
authors.lastname: de Silva
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D003062:Codon / Q000235:genetics; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D008239:Lysine / Q000235:genetics; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics; D016875:tau Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon; C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D008239:Lysine