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

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.