S.N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata, India.
Department of Neuromedicine, Bangur Institute of Neurosciences, Institute of Postgraduate Medical Education & Research, Kolkata, India.
Indian J Med Res. 2020 Jun;151(6):592-597. doi: 10.4103/ijmr.IJMR_25_18.
BACKGROUND & OBJECTIVES: Parkinsonian disorder, including Parkinson's disease (PD), is an aetiologically complex neurodegenerative disorder. Mutations in leucine-rich repeat kinase 2 (LRRK2) gene have been implicated in an autosomal dominant form of PD with variable penetrance. The identification of a common LRRK2 variant (p.Gly2019Ser) in dementia with Lewy bodies indicated its potential role in Parkinsonian disorder. The current study was aimed to identify the p.Gly2019Ser variant in Indian patients with Parkinsonian disorder.
The patient group consisting of 412 classical PD patients, 107 PD patients with cognitive impairment, 107 patients with Parkinson plus syndrome and 200 unrelated controls were recruited from eastern part of India. The allele representing p.Gly2019Ser variant was screened by polymerase chain reaction followed by restriction fragment length polymorphism analysis.
The p.Gly2019Ser variant was identified in an East Indian young-onset female PD patient in a heterozygous state having several motor and autonomic problems without disturbed cognition. Her younger brother, sister and elder son harbouring the same mutation were asymptomatic carriers for the variant. However, the influence of DNM3 on decreased disease onset in this family was not clear.
INTERPRETATION & CONCLUSIONS: Identification of the p.Gly2019Ser variant in only one patient among a large number of Indian patients (n=626) with Parkinsonian disorder in our study suggests a limited role of the LRRK2 variant towards disease pathogenesis.
帕金森病（PD）等帕金森氏症是一种病因复杂的神经退行性疾病。富含亮氨酸重复激酶 2（LRRK2）基因突变与具有可变外显率的常染色体显性形式的 PD 有关。在路易体痴呆中发现常见的 LRRK2 变异（p.Gly2019Ser）表明其在帕金森氏症中可能具有作用。本研究旨在鉴定印度帕金森氏症患者中的 p.Gly2019Ser 变异。
从印度东部招募了 412 名经典 PD 患者、107 名 PD 伴认知障碍患者、107 名帕金森综合征患者和 200 名无关对照者组成患者组。通过聚合酶链反应（PCR）随后进行限制性片段长度多态性分析筛选等位基因代表 p.Gly2019Ser 变异。
在一名东印度年轻起病的 PD 女性患者中发现了 p.Gly2019Ser 变异，该患者为杂合子状态，存在多种运动和自主神经问题，但认知功能未受影响。携带相同突变的她的弟弟、妹妹和哥哥为该变异的无症状携带者。然而，DNM3 对该家族中疾病发病延迟的影响尚不清楚。
在我们的研究中，在大量印度帕金森氏症患者（n=626）中仅发现 1 名患者存在 p.Gly2019Ser 变异，表明 LRRK2 变异对疾病发病机制的作用有限。
