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PSEN1 G417S mutation in a Chinese pedigree causing early-onset parkinsonism with cognitive impairment.
- Source :
-
Neurobiology of aging [Neurobiol Aging] 2022 Jul; Vol. 115, pp. 70-76. Date of Electronic Publication: 2022 Apr 11. - Publication Year :
- 2022
-
Abstract
- Presenilin 1 (PSEN1) mutations are a major cause of familial Alzheimer's disease. The pathogenic variant, PSEN1 p.G417S, has been reported to be associated with spastic paraparesis and cotton wool plaques in Japan. Here, we report a 3 generation Chinese pedigree that included 10 patients presenting with early-onset and rapid progression of parkinsonism with cognitive impairment in their third or fourth decade of life. Three additional living patients developed different degrees of cognitive impairment, without movement disorders. Magnetic resonance imaging of the brain showed white matter hyperintensities, multiple microbleeds, and enlarged perivascular spaces. Whole exome sequencing analysis of the proband detected the mutation, p.G417S, in PSEN1, which was completely co-segregated with the disease phenotype within the family by Sanger sequencing. 3D protein structures predicted that the mutation might influence contact with the lipid membrane and the interaction with beta-catenin. Our study provides insights into the heterogeneity in clinical presentation and imaging associated with mutations in PSEN1.<br /> (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Subjects :
- China
Humans
Mutation genetics
Pedigree
Presenilin-1 genetics
Alzheimer Disease diagnostic imaging
Alzheimer Disease genetics
Alzheimer Disease metabolism
Cognitive Dysfunction genetics
Parkinsonian Disorders complications
Parkinsonian Disorders diagnostic imaging
Parkinsonian Disorders genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1558-1497
- Volume :
- 115
- Database :
- MEDLINE
- Journal :
- Neurobiology of aging
- Publication Type :
- Academic Journal
- Accession number :
- 35489321
- Full Text :
- https://doi.org/10.1016/j.neurobiolaging.2022.03.016