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

Jussi O T Sipilä; Laura Kytövuori; Tuomas Rauramaa; Hugo Rauhamaa; Valtteri Kaasinen; Kari Majamaa

doi:10.1038/s41531-023-00501-4

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

NPJ Parkinsons Dis. 2023 Apr 5;9(1):53. doi: 10.1038/s41531-023-00501-4.

Authors

Jussi O T Sipilä^{1

2}, Laura Kytövuori^{3

4}, Tuomas Rauramaa⁵, Hugo Rauhamaa^{3

4}, Valtteri Kaasinen^{6

7}, Kari Majamaa^{3

4}

Affiliations

¹ Clinical Neurosciences, University of Turku, Turku, Finland. jussi.sipila@utu.fi.
² Department of Neurology, Siun Sote North Karelia Central Hospital, Joensuu, Finland. jussi.sipila@utu.fi.
³ Research Unit of Clinical Medicine and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
⁴ Neurocenter, Neurology, Oulu University Hospital, Oulu, Finland.
⁵ Unit of Pathology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
⁶ Clinical Neurosciences, University of Turku, Turku, Finland.
⁷ Neurocenter, Turku University Hospital, Turku, Finland.

Abstract

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.