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

O'Connor A., Abel E., Fraser MR., Ryan NS., Jiménez DA., Koriath C., Chávez-Gutiérrez L., Ansorge O., Mummery CJ., Lashley T., Rossor MN., Polke JM., Mead S., Fox NC.

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.

DOI

10.1016/j.neurobiolaging.2021.01.032

Type

Journal article

Publication Date

2021-07-01T00:00:00+00:00

Volume

103

Pages

137.e1 - 137.e5

Keywords

Dementia, Early-onset Alzheimer's disease, Familial Alzheimer's disease, Novel mutation, PSEN1 mutation, Alzheimer Disease, Dementia, Female, Humans, INDEL Mutation, Male, Mutagenesis, Insertional, Myoclonus, Presenilin-1, Seizures

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