Role of LRRK2 variant p.Gly2019Ser in patients with Parkinsonism
Dipanwita Sadhukhan1, Arindam Biswas1, Arunima Bhaduri1, Neelanjana Sarkar1, Atanu Biswas2, Shyamal K Das2, Tapas K Banerjee3, Kunal Ray4, Jharna Ray1
1 S.N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata, India
2 Department of Neuromedicine, Bangur Institute of Neurosciences, Institute of Postgraduate Medical Education & Research, Kolkata, India
3 National Neurosciences Centre Calcutta, Kolkata, India
4 Academy of Scientific & Innovative Research, New Delhi, India
Dr Jharna Ray
S.N. Pradhan Centre for Neurosciences, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700 019, West Bengal
Source of Support: The study was supported by the Department of Science & Technology (DST)-PURSE, a grant from the DST-CSI Programme (SR/CSI/89/2010) to the last author (JR). The second author (AB) was supported by a postdoctoral fellowship from the same Research Initiative Programme (SR/CSI/PDF-32/2014 and DST/CSRI-P/2017/22), and the first author (DS) was supported by a predoctoral fellowship from the University Grants Commission, New Delhi, Conflict of Interest: None
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.
Methods: 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.
Results: 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.