Division of Molecular Biology and Human Genetics, Faculty of Health Sciences, University of Stellenbosch, Cape Town, South Africa.
Parkinsonism Relat Disord. 2012 Jan;18(1):89-92. doi: 10.1016/j.parkreldis.2011.09.022. Epub 2011 Oct 12.
The molecular basis of Parkinson's disease (PD) has been extensively studied in numerous population groups over the past decade. However, very little is known of the molecular etiology of PD in the South African population. We aimed to assess the genetic contribution of parkin mutations to PD pathology by determining the frequency of both point mutations and exon rearrangements in all 12 exons of the parkin gene in a group of 229 South African patients diagnosed with PD. This was done by performing high resolution melt (HRM) as well as multiplex ligation-dependent probe amplification (MLPA) analyses. In total, seven patients (3.1%; 7/229) had either compound heterozygous or homozygous mutations in parkin, and seven patients (3.1%) had heterozygous sequence variants. Two of the patients with parkin mutations are of Black African ancestry. Reverse-transcription PCR on lymphocytes obtained from two patients verified the presence of parkin mutations on both alleles. In conclusion, the present study reveals that mutations in the parkin gene are not a major contributor to PD in the South African population. Further investigations of the molecular etiology of PD in the unique South African population, particularly the Black African and mixed ancestry sub-populations, are warranted.
在过去的十年中，许多人群的研究都广泛地探讨了帕金森病（PD）的分子基础。然而，对于南非人群的 PD 的分子病因学却知之甚少。我们旨在通过确定 229 名被诊断为 PD 的南非患者的 parkin 基因的所有 12 个外显子中的点突变和外显子重排的频率，来评估 parkin 突变对 PD 病理学的遗传贡献。通过进行高分辨率熔解（HRM）和多重连接依赖性探针扩增（MLPA）分析来完成此任务。总共有 7 名患者（3.1%；7/229）具有 parkin 的复合杂合或纯合突变，而 7 名患者（3.1%）具有杂合序列变异。两名具有 parkin 突变的患者来自非洲黑人血统。从两名患者的淋巴细胞中进行的逆转录 PCR 验证了 parkin 突变在两个等位基因上的存在。总之，本研究表明，parkin 基因中的突变不是南非人群中 PD 的主要原因。需要对独特的南非人群，特别是黑人非洲和混合血统亚人群的 PD 的分子病因学进行进一步研究。
