Laboratory of Neurogenetics, Parkinson's Disease and Cerebrovascular Disease, University Hospital Habib Bourguiba, Sfax, Tunisia.
Institut du Cerveau et de la Moelle épinière, INSERM U1127, Sorbonne Université, UPMC Paris VI Univ. UMR_S1127, CNRS UMR 7225, Paris, France.
Acta Neurol Scand. 2018 Nov;138(5):425-431. doi: 10.1111/ane.12996. Epub 2018 Jul 10.
The LRRK2-G2019S mutation is the most common cause of Parkinson's disease (PD) in North Africa. G2019S-PD has been described as similar to idiopathic with minor clinical differences. The aim of this study was to determine the G2019S-related phenotype and to investigate gender and gene dosage effects on clinical features of G2019S carriers.
The G2019S mutation was screened in 250 Tunisian patients with PD. Twenty-four patients carrying mutations in other PD genes were excluded. Logistic regression models were used to compare clinical features between the studied groups.
G2019S carriers (107 cases) and non-carriers (119 cases) were similar in disease duration, levodopa doses, and gender and phenotype distributions. However, carriers had a younger age at examination, higher level of education, and were more likely to report family history of PD and to develop PD at earlier age (P = 0.017). Adjusted for age, sex, disease duration, levodopa-equivalent dose and educational level, MMSE scores remained significantly higher (adjust P = 0.019) and UPDRS-III scores were lower (adjust P = 0.012) in the G2019S carriers than non-carriers. Demographic characteristics of men and women with G2019S mutation were similar, but men had higher level of education, better cognition (adjust P-value for educational level = 0.042) and less tendency towards depression than females (adjust P = 0.046). Furthermore, PD phenotype did not differ between the homozygous and heterozygous G2019S carriers.
In this study, G2019S carriers had a more benign phenotype than non-carriers. Cognitive impairment and depression were less common in G2019S male carriers compared with females. In addition, we found that LRRK2 gene dosage does not influence the severity of PD.
LRRK2-G2019S 突变是北非最常见的帕金森病（PD）病因。已描述 G2019S-PD 与特发性疾病相似，仅有轻微的临床差异。本研究旨在确定 G2019S 相关表型，并研究性别和基因剂量对 G2019S 携带者临床特征的影响。
在 250 例突尼斯 PD 患者中筛查 G2019S 突变。排除携带其他 PD 基因突变的 24 例患者。使用逻辑回归模型比较研究组之间的临床特征。
G2019S 携带者（107 例）和非携带者（119 例）在疾病持续时间、左旋多巴剂量以及性别和表型分布方面相似。然而，携带者的检查年龄更小，教育程度更高，更有可能报告 PD 家族史，并且更早发病（P=0.017）。在校正年龄、性别、疾病持续时间、左旋多巴等效剂量和教育程度后，MMSE 评分在 G2019S 携带者中仍显著更高（调整后 P=0.019），UPDRS-III 评分更低（调整后 P=0.012）。G2019S 突变男性和女性的人口统计学特征相似，但男性教育程度更高，认知能力更好（调整教育水平的 P 值=0.042），且抑郁倾向低于女性（调整后 P=0.046）。此外，G2019S 纯合子和杂合子携带者的 PD 表型无差异。
在本研究中，G2019S 携带者的表型比非携带者更良性。与女性相比，G2019S 男性携带者认知障碍和抑郁的发生率较低。此外，我们发现 LRRK2 基因剂量不影响 PD 的严重程度。
