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

Antoinette O'Connor; Emily Abel; M R Fraser; Natalie S Ryan; Daniel A Jiménez; Carolin Koriath; Lucía Chávez-Gutiérrez; Olaf Ansorge; Catherine J Mummery; Tammaryn Lashley; Martin N Rossor; James M Polke; Simon Mead; Nick C Fox

doi:10.1016/j.neurobiolaging.2021.01.032

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

Neurobiol Aging. 2021 Jul:103:137.e1-137.e5. doi: 10.1016/j.neurobiolaging.2021.01.032. Epub 2021 Feb 5.

Authors

Affiliations

¹ Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK.
² UK Dementia Research Institute at UCL, London, UK.
³ Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK.
⁴ MRC Prion Unit at UCL, UCL Institute of Prion Diseases, London, UK.
⁵ VIB-KU Leuven Centre for Brain and Disease Research, Leuven, Belgium; Department of Neurosciences, Leuven Research Institute for Neuroscience and Disease (LIND), KU Leuven, Leuven, Belgium.
⁶ Academic Unit of Neuropathology, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
⁷ Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK; Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
⁸ Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK.
⁹ MRC Prion Unit at UCL, UCL Institute of Prion Diseases, London, UK; National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK.
¹⁰ Dementia Research Centre, UCL Queen Square Institute of Neurology, London, UK; UK Dementia Research Institute at UCL, London, UK. Electronic address: n.fox@ucl.ac.uk.

PMID: 33648786
DOI: 10.1016/j.neurobiolaging.2021.01.032

Abstract

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.

Keywords: Dementia; Early-onset Alzheimer's disease; Familial Alzheimer's disease; Novel mutation; PSEN1 mutation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / genetics*
Dementia / genetics
Female
Humans
INDEL Mutation / genetics
Male
Mutagenesis, Insertional / genetics*
Myoclonus / genetics*
Presenilin-1 / genetics*
Seizures / genetics*

Substances

PSEN1 protein, human
Presenilin-1

Abstract

Publication types

MeSH terms

Substances

Grants and funding