Gaucher unit, Shaare Zedek Medical Center, Jerusalem, Israel.
Faculty of Medicine, Hebrew University of Jerusalem, Israel.
J Parkinsons Dis. 2021;11(2):615-618. doi: 10.3233/JPD-202422.
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.
帕金森病（PD）相关 GBA 致病性变异的低外显率表明存在修饰基因。具有 GBA 变异的某些家族中的 PD 病例群将为这些修饰基因的临床相关性提供有力证据。我们研究了 8 个非帕金森病、GBA-N370S 纯合子、戈谢病先证者的家族树，这些先证者有多例 PD。不同 GBA 变异与 PD 风险的差异通过变异纯合性得到平衡。在这些家族中，所有 PD 病例均源自先证者父母中的一方。这一观察结果为遗传修饰物在 GBA 变异携带者中决定 PD 风险提供了直接的流行病学证据。
