Parkinson’s Clustering in Families of Non-Neuronopathic N370S GBA Mutation Carriers Indicates the Presence of Genetic Modifiers

Article type: Short Communication

Authors: Dinur, Tama^a | Becker-Cohen, Michal^a | Revel-Vilk, Shoshana^{a; b} | Zimran, Ari^{a; b} | Arkadir, David^{b; c; *}

Affiliations: [a] Gaucher unit, Shaare Zedek Medical Center, Jerusalem, Israel | [b] Faculty of Medicine, Hebrew University of Jerusalem, Israel | [c] Department of Neurology, Hadassah Medical Center, Jerusalem, Israel

Correspondence: [*] Correspondence to: David Arkadir, MD, PhD, Hadassah Medical Center, POB 12000, Jerusalem 91120, Israel. E-mail: arkadir@hadassah.org.il.

Abstract: Low penetrance of Parkinson’s disease (PD) associated with GBA pathogenic variants indicates the presence of modifiers genes. Clusters of PD cases in certain families with GBA variants would serve as a strong evidence for the clinical relevance of such modifiers. We studied eight family trees of non-Parkinsonian, GBA-N370S homozygote, Gaucher probands, with multiple cases of PD. Differences in PD risk associated with different GBA variants were balanced by variant homozygosity. In these families, all PD cases stemmed from only one of the proband’s parents. This observation provides a direct epidemiological evidence for genetic modifiers determining PD risk in GBA variant carriers.

Keywords: Parkinson’s disease, Gaucher disease, allele penetrance, pedigrees

DOI: 10.3233/JPD-202422

Journal: Journal of Parkinson's Disease, vol. 11, no. 2, pp. 615-618, 2021