title: Molecular pathogenesis of Parkinson's disease: identification of mutations in the Parkin gene in Indian patients.
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 47+/-14 (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.
authors.affiliation: S.N. Pradhan Centre for Neurosciences, University of Calcutta, 244B, A.J.C. Bose Road, Kolkata 700 020, India.
authors.forename: Arindam
authors.initials: A
authors.lastname: Biswas
authors.forename: Arnab
authors.initials: A
authors.lastname: Gupta
authors.forename: Tufan
authors.initials: T
authors.lastname: Naiya
authors.forename: Gautami
authors.initials: G
authors.lastname: Das
authors.forename: Rajarshi
authors.initials: R
authors.lastname: Neogi
authors.forename: Somnath
authors.initials: S
authors.lastname: Datta
authors.forename: Subhas
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Shyamal K
authors.initials: SK
authors.lastname: Das
authors.forename: Kunal
authors.initials: K
authors.lastname: Ray
authors.forename: Jharna
authors.initials: J
authors.lastname: Ray
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010300:Parkinson Disease / Q000208:ethnology* / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein