Tan Eng-King, Yew Kenneth, Chua Eva, Puvan K, Shen Hui, Lee Esther, Puong Kim-Yoong, Zhao Yi, Pavanni Ratnagopal, Wong Meng-Cheong, Jamora Dominic, de Silva Deidre, Moe Kyaw-Thu, Woon Fung-Peng, Yuen Yih, Tan Louis
Division of Research, SingHealth, Singapore.
Mov Disord. 2006 Jun;21(6):789-93. doi: 10.1002/mds.20810.
Pathogenic PINK1 mutations have been described in PARK6-linked Parkinson's disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early-onset Parkinson's disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1-positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon-intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1-positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.
在亚洲裔帕金森病（PD）患者中，已发现与早发性帕金森病（EOPD）相关的致病性PINK1突变。然而，关于散发性早发性帕金森病（EOPD）亚洲患者中PINK1突变频率的数据尚缺。本研究的目的是报告在一个由华裔、马来人和印度人组成的亚洲队列中散发性EOPD的PINK1突变频率，并着重介绍一名出现不宁腿症状的PINK1阳性患者。纳入了该国两所主要三级医疗机构运动障碍门诊的80例连续散发性EOPD患者。我们使用特异性引物对PINK1的所有编码区和外显子-内含子连接区进行了序列分析。此外，我们对一组散发性PD患者和对照中分析检测到的多态性进行了基因分型。在3例患者中发现了推定激酶结构域中的3种不同突变（2种纯合无义突变和1种杂合错义突变），在我们的EOPD队列中PINK1突变频率为3.7%。在200名健康对照中均未发现所有这些突变。一名患有新型纯合无义PINK1突变的患者异常地出现了不宁腿症状。另外，对一组散发性PD患者和对照中4种PINK1多态性频率的分析未发现任何显著差异。我们强调在一个亚洲（华裔、马来人和印度人）EOPD队列中PINK1突变频率为3.7%。与PINK1阳性患者相关的表型谱可能比先前报道的更广泛。在我们的人群中，PINK1多态性似乎不会调节PD的风险。
