Absence of Commonly Reported Leucine-Rich Repeat Kinase 2 Mutations in Eastern Indian Parkinson's Disease Patients

Abstract

We conclude that these mutations are rare causes of PD in the Eastern Indian population and, therefore, of little help for genetic counseling and diagnostic purposes.

Movement disorders: Indian scenario: A clinico-genetic review

“…[44] Parkinson's Disease Eighteen genetic loci with 13 underlying genes have been identified till date for PD, however, only 6 genes [Alpha-synuclein (SNCA), Leucine rich repeat kinase-2 (LRRK2), Parkin, PTEN induced putative kinase 1 (PINK1), DJ-1, ATPase type 13A2 (ATP13A2)] could be conclusively proved to be causal towards the disease. [45] In India, candidate gene studies have been performed on SNCA, [46,47] Parkin, [48][49][50][51][52] PINK1, [53] DJ-1, [54,55] and LRRK2 [47,[56][57][58][59] only [ In India studies to understand the molecular basis of PD is rapidly getting pace. A number of association studies have been reported on the candidate [53,60] as well as the susceptibility genes involved in dopamine metabolism, [61][62][63] xenobiotic metabolism, [64,65] neuronal cytoskeletal stability [66,67] etc., from different parts of India.…”

Evaluation of the Role of LRRK2 Gene in Parkinson’s Disease in an East Indian Cohort

“…Other common mutations like p.Arg1441Cys, p.Arg1441Gly, p.Arg1441His, p.Tyr1699Cys have been studied in the North and East Indian populations (including the present study). Among East Indians we and Sanyal et al [15] have examined for an additional mutation, p.Tyr1699Cys but did not find one. Our result on common mutation screening in LRRK2 is consistent with 3 previous studies suggesting that at least previously reported mutations in other populations must be rare, if not absent, among Indians.…”

“…Studies on LRRK2 have been done on a few selected variants in the Indian population encompassing northern [13], southern [21] and eastern regions [15] of the country. Among these variants p.Gly2019Ser has been extensively studied in all the 3 regions of India (including the present one).…”

“…In India there have been 3 studies on LRRK2 from different geographical regions (north, east and south); however these studies have only searched for the most prevalent (p.G2019S) or common mutations and have not explored the role of LRRK2 as a susceptibility gene in PD [13,15,21]. Herein, we report on a comprehensive, haplotype-tagging SNP approach to determine whether LRRK2 is a susceptibility gene for PD in an East Indian cohort.…”

Evaluation of PARKIN gene variants in West Bengal Parkinson’s disease patients

“…None of these individuals harbored any pathogenic mutations in LRRK2 and DJ-1 genes. 13,14 On screening these patients for nucleotide variants in all the12 exons and flanking regions of Parkin gene, a total of 11 changes were identified (rs2075923(IVS2+25T4C), Figure 1), which include two novel changes and nine reported changes (Table 2). Among the sequence variants, five missense mutations (Table 2) were found only in the patients under study, but none in the 150 control individuals selected based on lack of any neurological symptoms.…”