A multiplex pedigree with pathologically confirmed multiple system atrophy and Parkinson's disease with dementia.
Parkinson’s disease
Parkinson’s disease with dementia
genetics
multiple system atrophy
multiplex pedigree
Journal
Brain communications
ISSN: 2632-1297
Titre abrégé: Brain Commun
Pays: England
ID NLM: 101755125
Informations de publication
Date de publication:
2022
2022
Historique:
received:
14
02
2022
revised:
12
05
2022
accepted:
01
07
2022
entrez:
20
7
2022
pubmed:
21
7
2022
medline:
21
7
2022
Statut:
epublish
Résumé
Multiple system atrophy is considered a sporadic disease, but neuropathologically confirmed cases with a family history of parkinsonism have been occasionally described. Here we report a North-Bavarian (colloquially, Lion's tail region) six-generation pedigree, including neuropathologically confirmed multiple system atrophy and Parkinson's disease with dementia. Between 2012 and 2020, we examined all living and consenting family members of age and calculated the risk of prodromal Parkinson's disease in those without overt parkinsonism. The index case and one paternal cousin with Parkinson's disease with dementia died at follow-up and underwent neuropathological examination. Genetic analysis was performed in both and another family member with Parkinson's disease. The index case was a female patient with cerebellar variant multiple system atrophy and a positive maternal and paternal family history for Parkinson's disease and dementia in multiple generations. The families of the index case and her spouse were genealogically related, and one of the spouse's siblings met the criteria for possible prodromal Parkinson's disease. Neuropathological examination confirmed multiple system atrophy in the index case and advanced Lewy body disease, as well as tau pathology in her cousin. A comprehensive analysis of genes known to cause hereditary forms of parkinsonism or multiple system atrophy lookalikes was unremarkable in the index case and the other two affected family members. Here, we report an extensive European pedigree with multiple system atrophy and Parkinson`s disease suggesting a complex underlying α-synucleinopathy as confirmed on neuropathological examination. The exclusion of known genetic causes of parkinsonism or multiple system atrophy lookalikes suggests that variants in additional, still unknown genes, linked to α-synucleinopathy lesions underlie such neurodegenerative clustering.
Identifiants
pubmed: 35855480
doi: 10.1093/braincomms/fcac175
pii: fcac175
pmc: PMC9291376
doi:
Types de publication
Journal Article
Langues
eng
Pagination
fcac175Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.
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