Division of Molecular Biology and Human Genetics, University of Stellenbosch, 4th Floor Fisan Building, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa.
J Neural Transm (Vienna). 2010 Jul;117(7):847-53. doi: 10.1007/s00702-010-0423-6. Epub 2010 Jun 11.
Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) are the most significant genetic cause of Parkinson's disease (PD). The exact function of LRRK2 is currently unknown but the presence of multiple protein interaction domains including WD40 and ankyrin indicates that it may act a scaffold for assembly of a multi-protein signaling complex. The G2019S mutation in LRRK2 represents the most clinically relevant PD-causing mutation and has been found in both familial and sporadic forms of the disorder. This mutation is situated in the highly conserved kinase MAPKKK domain, and has been found in up to 40% of PD patients from North African Arabic, 30% of Ashkenazi Jewish and approximately 10% of Portuguese and Spanish populations. Although extensively investigated in numerous European and North American populations, studies on the frequency of G2019S in African countries have been rare. The present study is the first on the South African population. High-resolution melt analysis was used to identify the G2019S mutation and it was found in 2% (4/205) of the patients studied. G2019S was not found in any of the Black PD patients screened. In all four G2019S-positive probands the mutation was shown to be present on the common haplotype referred to as haplotype 1. This reveals that the four South African G2019S-positive probands (three Caucasian and one of mixed ancestry) share a common ancestor with the other haplotype 1-associated families reported worldwide.
LRRK2 基因中的亮氨酸丰富重复激酶 2 突变是帕金森病（PD）最主要的遗传病因。LRRK2 的确切功能目前尚不清楚，但存在多个蛋白相互作用结构域，包括 WD40 和锚蛋白，表明它可能作为组装多蛋白信号复合物的支架。LRRK2 中的 G2019S 突变代表了最具临床相关性的 PD 致病突变，在家族性和散发性疾病中均有发现。该突变位于高度保守的激酶 MAPKKK 结构域，在北非阿拉伯裔的高达 40%的 PD 患者、阿什肯纳兹犹太裔的 30%的患者以及约 10%的葡萄牙裔和西班牙裔患者中均有发现。尽管在许多欧洲和北美人群中进行了广泛研究，但对非洲国家 G2019S 频率的研究很少。本研究是针对南非人群的首次研究。高分辨率熔解分析用于鉴定 G2019S 突变，在研究的 205 名患者中发现了 2%（4/205）的患者携带该突变。在筛查的黑人 PD 患者中未发现 G2019S。在所有 4 名 G2019S 阳性先证者中，该突变均存在于称为 1 号单倍型的常见单倍型上。这表明，这 4 名南非 G2019S 阳性先证者（3 名白人和 1 名混合血统）与全球报告的其他 1 号单倍型相关家族具有共同的祖先。
