Tan E K, Skipper Lisa, Chua Eva, Wong Meng-Cheong, Pavanni Ratnagopal, Bonnard Carine, Kolatkar Prasanna, Liu Jian-Jun
Department of Neurology, Singapore General Hospital, Singapore.
Mov Disord. 2006 Jul;21(7):997-1001. doi: 10.1002/mds.20875.
The pleomorphic pathology of postmortem LRRK2-positive patients and the frequent association with late-onset Parkinson's disease (LOPD) symptoms suggest that LRRK2 mutations may play a role in Parkinson's Plus disorders and LOPD. Published studies primarily focus on the common G2019S mutation. Analysis of a spectrum of LRRK2 mutations in Parkinson's Plus disorders has yet to be reported. We investigated 14 leucine-rich repeat kinase 2 (LRRK2) mutations in a cohort of Parkinson's Plus disorders and LOPD. A total of 458 patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal ganglionic degeneration (CBGD), atypical Parkinsonism (AP), and LOPD were screened for 14 mutations that span exons 19 to 41 of the LRRK2 gene. Among the LOPD cases, 1 patient was found to harbor the R1441C mutation. He presented with typical features of PD at age of 58 years old and responded well to levodopa. We did not detect any of the 14 mutations in PSP, MSA, CBGD, and AP patients. We highlight the first case of LRRK2 R1441C mutation in late onset sporadic PD of non-European ancestry. Furthermore, extensive mutational screen found LRRK2 mutations to be rare among patients who presented with PSP, MSA, CBGD, and AP.
尸检时LRRK2呈阳性的患者的多形性病理学以及与晚发性帕金森病（LOPD）症状的频繁关联表明，LRRK2突变可能在帕金森叠加综合征和LOPD中起作用。已发表的研究主要集中在常见的G2019S突变上。尚未有关于帕金森叠加综合征中一系列LRRK2突变分析的报道。我们在一组帕金森叠加综合征和LOPD患者中研究了14种富含亮氨酸重复激酶2（LRRK2）突变。对总共458例进行性核上性麻痹（PSP）、多系统萎缩（MSA）、皮质基底节变性（CBGD）、非典型帕金森病（AP）和LOPD患者进行了筛查，以检测LRRK2基因第19至41外显子的14种突变。在LOPD病例中，发现1例携带R1441C突变。他在58岁时表现出典型的帕金森病特征，对左旋多巴反应良好。我们在PSP、MSA、CBGD和AP患者中未检测到这14种突变中的任何一种。我们强调了非欧洲血统晚发性散发性帕金森病中首例LRRK2 R1441C突变。此外，广泛的突变筛查发现，在表现为PSP、MSA、CBGD和AP的患者中，LRRK2突变很少见。
