Parkinsonism and Related Disorders 12 (2006) 420–426 Molecular pathogenesis of Parkinson’s disease: Identification of mutations in the Parkin gene in Indian patients Arindam Biswas a , Arnab Gupta b , Tufan Naiya a , Gautami Das a , Rajarshi Neogi b , Somnath Datta b , Subhas Mukherjee c , Shyamal K. Das d , Kunal Ray b , Jharna Ray a,Ã a S.N. Pradhan Centre for Neurosciences, University of Calcutta, 244B, A.J.C. Bose Road, Kolkata 700 020, India b Human Genetics & Genomics Division, Indian Institute of Chemical Biology, Kolkata, India c Medical College and Hospital, Kolkata, India d Bangur Institute of Neurology, Kolkata, India Received 28 September 2005; received in revised form 4 April 2006; accepted 8 April 2006 Abstract Parkinson’s disease (PD), the second most common neurodegenerative disorder, affects at least 1% of the population over the age of 50. However, very little information is available regarding the molecular basis of PD among Indians. Since the largest number of mutations have been detected in the Parkin gene among all known PD loci, we aim to use Parkin as the candidate gene to assess its role in PD-related pathogenesis in Indian patients. A total of 138 PD patients, with the mean age of onset being 47714 (age range, 5–77 years), and 100 controls were recruited for the study from eastern India. Parkin mutations were detected by amplification of exons of the gene along with the flanking splice junctions by polymerase chain reaction, single-stranded conformation polymorphism and DNA sequencing. A total of 18 nucleotide variants including six novel changes were detected. These include five missense mutations (Gln34Arg, Arg42Cys, Arg42His, Tyr143Cys and Arg334Cys) detected in eight patients in heterozygous condition and a homozygous deletion encompassing exons 3 and 4 in two sibs affected with PD. Clinical features of the Parkin mutants were compared. Among eastern Indian PD patients, mutation in Parkin was identified in 7.24% cases. r 2006 Elsevier Ltd. All rights reserved. Keywords: Parkin; Parkinson’s disease; PD 1. Introduction Parkinson’s Disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease af- fecting at least 1% of the population over age 50 [1–3]. The disease is progressive with mean age of onset being 55 years, and its incidence increases with age [4]. The hallmark of PD is the degeneration of nigrostriatal dopaminergic pathway. Depletion of brain dopamine initiates aberrant motor activities including rest tremor, rigidity, bradykinesia, postural instability and mask face. The prevalence of PD in North America and West European countries is 150–200 per 100,000 [5] and much lower in China, Japan and Africa (45–80 per 100,000). In India, PD affects around 14–27 per 100,000 but the incidence of the disease is much higher among the Parsis (328 per 100,000) living in India [6,7]. PD generally arises as sporadic condition but occasionally inherited in families both as an autosomal dominant or autosomal recessive trait. To date, 11 chromosomal loci (PARK1– PARK11) have been implicated for PD of which six causal genes have been identified, and one locus (PARK4), later found to have been assigned based on false linkage. Three genes a-Synuclein (SNCA), Ubiqui- tin carboxy-terminal hydrolase L-1 (UCHL-1), LRRK2 and three loci (on chromosomes 2p13, 1p32 and ARTICLE IN PRESS www.elsevier.com/locate/parkreldis 1353-8020/$ - see front matter r 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.parkreldis.2006.04.005 Ã Corresponding author. Tel.: +91 33 2223 2084; fax: +91 33 2223 3260. E-mail address: thisisjr@rediffmail.com (J. Ray).