Affiliations: [a] Gaucher unit, Shaare Zedek Medical Center, Jerusalem, Israel
| [b] Faculty of Medicine, Hebrew University of Jerusalem, Israel
Department of Neurology, Hadassah Medical Center, Jerusalem, Israel
Correspondence to: David Arkadir, MD, PhD, Hadassah Medical Center, POB 12000, Jerusalem 91120, Israel. E-mail: [email protected].
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.