Clinical and pathological features of an Alzheimer's disease patient with the MAPT Delta K280 mutation.
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.
Momeni
Parastoo
P
Laboratory of Neurogenetics, NIA, NIH Main Campus, Bethesda, MD 20892, USA.
Pittman
Alan
A
Lashley
Tammaryn
T
Vandrovcova
Jana
J
Malzer
Elke
E
Luk
Connie
C
Hulette
Christine
C
Lees
Andrew
A
Revesz
Tamas
T
Hardy
John
J
de Silva
Rohan
R
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
D003062:Codon; C054369:MAPT protein, human; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D008239:Lysine