van der Merwe Celia, Carr Jonathan, Glanzmann Brigitte, Bardien Soraya
Division of Molecular Biology & Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Division of Neurology, Tygerberg Hospital, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Neurosci Lett. 2016 Apr 21;619:168-71. doi: 10.1016/j.neulet.2016.03.028. Epub 2016 Mar 18.
Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. To date, a number of PD-causing genes have been found, including SNCA, LRRK2, VPS35, PARK2, PINK1, DJ-1, ATP13A2, and most recently CHCHD2. Mutations in these genes range from point mutations to larger exonic rearrangements including deletions and duplications. This study aimed to detect possible copy number variation (CNV) in the known PD-causing genes in a cohort of South African patients with PD. Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was performed on a total of 210 South African PD patients, and possible CNVs were verified using quantitative real time PCR. No homozygous or compound heterozygous exon rearrangements in the genes analysed were found in the patient group. A heterozygous PARK2 exon 4 deletion was found in a sporadic patient with an age at onset of 51 years. Sanger sequencing did not reveal any additional mutations in PARK2 in this patient. Combining our results with that of previous studies in a South African cohort, the frequency of exonic rearrangements in the known PD-causing genes is only 1.8% (8/439 patients). In conclusion, CNV in the known PD-causing genes are a rare cause of PD in a South African cohort, and there may be as yet unknown genetic causes of PD that are specific to patients of African ethnicity.
帕金森病（PD）是一种神经退行性运动障碍，其特征是中脑黑质中多巴胺能神经元的丧失。迄今为止，已经发现了许多导致PD的基因，包括SNCA、LRRK2、VPS35、PARK2、PINK1、DJ-1、ATP13A2，以及最近发现的CHCHD2。这些基因的突变范围从点突变到更大的外显子重排，包括缺失和重复。本研究旨在检测一组南非帕金森病患者中已知致病基因的可能拷贝数变异（CNV）。对总共210名南非帕金森病患者进行了多重连接依赖探针扩增（MLPA）分析，并使用定量实时PCR验证了可能的CNV。在患者组中未发现所分析基因的纯合或复合杂合外显子重排。在一名发病年龄为51岁的散发性患者中发现了杂合性PARK2外显子4缺失。桑格测序未发现该患者PARK2有任何其他突变。将我们的结果与南非队列中先前研究的结果相结合，已知致病基因中外显子重排的频率仅为1.8%（8/439例患者）。总之，已知致病基因中的CNV是南非队列中帕金森病的罕见病因，可能存在尚未明确的、特定于非洲裔患者的帕金森病遗传病因。
