{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T23:05:01Z","timestamp":1785020701316,"version":"3.55.0"},"reference-count":85,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T00:00:00Z","timestamp":1656892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008383","name":"Stichting ParkinsonFonds","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008383","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100018889","name":"Multiple System Atrophy Coalition","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100018889","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2019s tail region) six-generation pedigree, including neuropathologically confirmed multiple system atrophy and Parkinson\u2019s disease with dementia.<\/jats:p>\n               <jats:p>Between 2012 and 2020, we examined all living and consenting family members of age and calculated the risk of prodromal Parkinson\u2019s disease in those without overt parkinsonism. The index case and one paternal cousin with Parkinson\u2019s disease with dementia died at follow-up and underwent neuropathological examination. Genetic analysis was performed in both and another family member with Parkinson\u2019s disease. The index case was a female patient with cerebellar variant multiple system atrophy and a positive maternal and paternal family history for Parkinson\u2019s 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\u2019s 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 \u03b1-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 \u03b1-synucleinopathy lesions underlie such neurodegenerative clustering.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac175","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T14:48:37Z","timestamp":1656946117000},"source":"Crossref","is-referenced-by-count":7,"title":["A multiplex pedigree with pathologically confirmed multiple system atrophy and Parkinson\u2019s disease with dementia"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2854-4179","authenticated-orcid":false,"given":"Alessandra","family":"Fanciulli","sequence":"first","affiliation":[{"name":"Department of Neurology, Medical University of Innsbruck , Innsbruck , 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University Medical Center , Rotterdam , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Fevga","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC, University Medical Center , Rotterdam , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Windl","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Herms","sequence":"additional","affiliation":[{"name":"Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich , Munich , 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