Department of Genetics, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
J Neurol Sci. 2017 Oct 15;381:160-164. doi: 10.1016/j.jns.2017.08.3249. Epub 2017 Aug 24.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by remarkable phenotypic variability. Accumulated evidence points that the manifestation of PD clinical signs might be differentially modified by genetic factors, as mutations in LRRK2 and GBA genes. In this sense, the clarification of the genotype-phenotype correlations in PD has important implications in predicting prognosis and can contribute to the development of specific therapeutic approaches.
Here, we conducted the first comparative analysis of motor and non-motor features in 17 LRRK2 and 22 GBA mutation carriers and 93 non-carriers unrelated PD patients from Brazil, a highly admixed population.
Significant differences were found between the three groups. LRRK2 PD patients presented more occurrence of familiar history. Resting tremor was observed in a lower frequency in GBA mutation carries. In contrast, gait freezing and dysautonomia was present in lower frequencies in LRRK2 carriers. Besides that, LRRK2 and GBA mutation carriers showed a higher incidence of depressive symptoms and a younger age at onset, when compared to non-carriers.
Our results suggest that specific mutations in GBA and LRRK2 influence the clinical signs of the disease, with significant implications for handling of specific patient groups.
帕金森病（PD）是一种神经退行性疾病，其表型具有显著的可变性。越来越多的证据表明，PD 临床症状的表现可能受到遗传因素的不同影响，如 LRRK2 和 GBA 基因的突变。从这个意义上说，阐明 PD 的基因型-表型相关性对预测预后具有重要意义，并有助于开发特定的治疗方法。
在这里，我们对来自巴西的 17 名 LRRK2 突变携带者、22 名 GBA 突变携带者和 93 名非携带者的运动和非运动特征进行了首次比较分析，巴西是一个高度混合的人群。
三组之间存在显著差异。LRRK2 PD 患者家族史发生率更高。GBA 突变携带者中静止性震颤的发生频率较低。相反，LRRK2 携带者中步态冻结和自主神经功能障碍的发生频率较低。此外，与非携带者相比，LRRK2 和 GBA 突变携带者表现出更高的抑郁症状发生率和更年轻的发病年龄。
我们的研究结果表明，GBA 和 LRRK2 中的特定突变影响疾病的临床症状，这对特定患者群体的处理具有重要意义。
