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A severe neurodegenerative disease with Lewy bodies and a mutation in the glucocerebrosidase gene.

Jussi O T SipiläLaura KytövuoriTuomas RauramaaHugo RauhamaaValtteri KaasinenKari Majamaa
Published in: NPJ Parkinson's disease (2023)
Several heterozygous variants of the glucocerebrosidase gene (GBA1) have been reported to increase the risk of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). GBA1-associated PD has been reported to be more severe than idiopathic PD, and more deleterious variants are associated with more severe clinical phenotypes. We report a family with a heterozygous p.Pro454Leu variant in GBA1. The variant was associated with a severe and rapidly progressive neurodegenerative disease with Lewy bodies that were clinically and pathologically diverse. Pathogenicity prediction algorithms and evolutionary analyses suggested that p.Pro454Leu is deleterious.
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