Identification of a rare presenilin 1 single amino acid deletion mutation (F175del) with unusual amyloid-β processing effects
Publisher DOI
PubMed ID
31627977
Abstract
We report the novel presenilin 1 (PSEN1) single amino acid deletion mutation F175del. Comprehensive clinical work-up, including cerebral MRI, FDG-PET, and CSF analysis, was performed in a male who had developed forgetfulness at the age of 39. Alzheimer's disease dementia was diagnosed according to established criteria. The index patient manifested rapid progressive dementia, seizures, and myoclonus, and a Pisa syndrome as a side effect of donepezil treatment. The PSEN1 mutation F175del was found on genetic testing. It was rendered very likely pathogenic as amyloid-β (Aβ) peptide 42 was elevated in a cell culture model compared to presenilin 1 wild-type controls. An additional, unusual increase in Aβ39 indicates a rarely observed product line deviation in the generation of the shorter Aβ species. Our observations extend the range of PSEN1 mutations to be considered in familial dementia. We demonstrate that deletion of a single conserved amino acid, which is very rare compared to missense mutations as the common cause for PSEN1-associated Alzheimer's disease, can lead to an unusual profile of Aβ species.
Date Issued
2019
Publication Type
Article
Subject(s)
Subjects
Alzheimer’s disease
•
Autosomal dominant
•
Genetics
•
Novel mutation
•
PSEN1
Language(s)
en
Author(s)
Vöglein, Jonathan | |
Willem, Michael | |
Trambauer, Johannes | |
Schönecker, Sonja | |
Dieterich, Marianne | |
Biskup, Saskia | |
Giudici, Camilla | |
Utz, Kathrin | |
Oberstein, Timo | |
Brendel, Matthias | |
Danek, Adrian | |
Steiner, Harald | |
Haass, Christian | |
Levin, Johannes |
Additional Credits
Journal
Neurobiology of aging
Publisher
Elsevier
ISSN
0197-4580
Access(Rights)
restricted