Institute of Genome Research, Vietnam Academy of Science and Technology, Hanoi, Vietnam.
Graduate University of Science and Technology, Vietnam Academy of Science and Technology, Hanoi, Vietnam.
Mol Genet Genomic Med. 2020 Oct;8(10):e1463. doi: 10.1002/mgg3.1463. Epub 2020 Aug 27.
Early-onset Parkinson's disease (EOPD) refers to that of patients who have been diagnosed or had onset of motor symptoms before age 50, accounting for 4% of Parkinson's disease patients. The PRKN and PINK1 genes, both involved in a metabolic pathway, are associated with EOPD.
To identify variants associated with EOPD, coding region of PARKIN and PINK1 genes in 112 patients and 112 healthy individuals were sequenced. Multiplex ligation-dependent probe amplification kit was used to determine EOPD patients that carried mutations in PRKN and PINK1 genes.
Three rare and three novel mutations in total of 14 variants of PARKIN and PINK1 were detected in the EOPD cohorts. Mutations of PRKN and PINK1 genes were found in five (4.4%) patients, which were four patients with compound heterozygous variants in the PRKN and one case with a homozygous mutation of the PINK1 gene. The novel mutations might reduce the stability of the PRKN and PINK1 protein molecules. The frequency of homozygous mutant genotype p.A340T of the PINK1 in the EOPD cohort was higher than in control (p = 0.0001, OR = 5.704), suggesting this variant might be a risk factor for EOPD. To the best of our knowledge, this is the first study of PRKN and PINK1 genes conducted on Vietnamese EOPD patients. These results might contribute to the genetic screening of EOPD in Vietnam.
早发性帕金森病（EOPD）是指患者在 50 岁之前被诊断或出现运动症状，占帕金森病患者的 4%。涉及代谢途径的 PRKN 和 PINK1 基因与 EOPD 有关。
为了鉴定与 EOPD 相关的变异，对 112 例患者和 112 名健康个体的 PARKIN 和 PINK1 基因的编码区进行了测序。使用多重连接依赖性探针扩增试剂盒来确定携带 PRKN 和 PINK1 基因突变的 EOPD 患者。
在 EOPD 队列中共检测到 14 种 PARKIN 和 PINK1 变体中的 3 种罕见和 3 种新突变。在 5 名（4.4%）患者中发现了 PRKN 和 PINK1 基因的突变，其中 4 名患者存在 PRKN 复合杂合变体，1 名患者存在 PINK1 基因的纯合突变。新的突变可能降低 PRKN 和 PINK1 蛋白分子的稳定性。PINK1 基因的纯合突变基因型 p.A340T 在 EOPD 队列中的频率高于对照组（p=0.0001，OR=5.704），提示该变体可能是 EOPD 的危险因素。据我们所知，这是对越南 EOPD 患者进行的 PRKN 和 PINK1 基因的首次研究。这些结果可能有助于越南 EOPD 的遗传筛查。
