A novel presenilin 1 duplication mutation (Ile168dup) causing Alzheimer's disease associated with myoclonus, seizures and pyramidal features

•A novel PSEN1 mutation (Ile168dup) causes pathologically proven Alzheimer's disease.•PSEN1 Ile168dup can manifest with seizures, myoclonus and pyramidal dysfunction.•Duplication and insertion/deletion mutations of PSEN1 can cause young onset dementia. Mutations in the Presenilin 1 (PSEN1) gene...

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Bibliographic Details
Published in:Neurobiology of aging 2021-07, Vol.103, p.137.e1-137.e5
Main Authors: O'Connor, Antoinette, Abel, Emily, Fraser, M.R., Ryan, Natalie S., Jiménez, Daniel A., Koriath, Carolin, Chávez-Gutiérrez, Lucía, Ansorge, Olaf, Mummery, Catherine J., Lashley, Tammaryn, Rossor, Martin N., Polke, James M., Mead, Simon, Fox, Nick C.
Format: Article
Language:English
Subjects:
Alzheimer Disease - genetics
Dementia
Dementia - genetics
Early-onset Alzheimer's disease
Familial Alzheimer's disease
Female
Humans
INDEL Mutation - genetics
Male
Mutagenesis, Insertional - genetics
Myoclonus - genetics
Novel mutation
Presenilin-1 - genetics
PSEN1 mutation
Seizures - genetics
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Summary:•A novel PSEN1 mutation (Ile168dup) causes pathologically proven Alzheimer's disease.•PSEN1 Ile168dup can manifest with seizures, myoclonus and pyramidal dysfunction.•Duplication and insertion/deletion mutations of PSEN1 can cause young onset dementia. Mutations in the Presenilin 1 (PSEN1) gene are the most common cause of autosomal dominant familial Alzheimer's disease. We report the clinical, imaging and postmortem findings of kindred carrying a novel duplication mutation (Ile168dup) in the PSEN1 gene. We interpret the pathogenicity of this novel variant and discuss the additional neurological features (pyramidal dysfunction, myoclonus and seizures) that accompanied cognitive decline. This report broadens the clinical phenotype of PSEN1 insertion mutations while also highlighting the importance of considering duplication, insertion and deletion mutations in cases of young onset dementia.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2021.01.032