title: Genetic screening reveals high frequency of PARK2 mutations and reduced Parkin expression conferring risk for Parkinsonism in North West India.
abstract: BACKGROUND
  Among several aetiological factors, PARK2 mutations are the most common cause of Parkinson disease (PD) that result in degeneration of dopaminergic neurons in the substantia nigra.
  
  
  METHODS
  In order to examine the contribution of PARK2 mutations and corresponding Parkin expression in blood of North West Indian PD patients, the authors screened 120,000 patients from 2001 to 2006 for features of PD using UK Parkinson disease society brain bank clinical diagnostic criteria (UKPDBBC), and tested PARK2 mutations in 69 of those that fulfilled this criteria. 43 controls lacking extrapyramidal signs were also analysed.
  
  
  RESULTS
  The PCR analysis revealed the occurrence of homozygous deletions in 28 of 69 samples analysed (40.5%) represented by exon-1 (15.9%), exon-3 (11.5%), and exon-12 (11.5%). Sequencing revealed point mutations in exon 4 and exon 9 in six of these patients (8.7%) including one novel missense Gly1083Trp mutation in one patient. Parkin estimation was done by combination of immunolocalisation and FACS analysis revealing reduced Parkin expression among PD patients. The mutations in exons 1, 3 and 12 among sporadic PD patients were found to be higher among younger onset variants (age<45 years). This report also constitutes the first evidence that PARK 2 mutations contribute to the aberration in Parkin expression in blood leading to PD.
authors.affiliation: Department of Neurology, Post Graduate Institute of Medical Education and Research, Sector-12 Chandigarh 160012, India. akshay1anand@rediffmail.com
authors.forename: Monika
authors.initials: M
authors.lastname: Vinish
authors.forename: Sudesh
authors.initials: S
authors.lastname: Prabhakar
authors.forename: Madhu
authors.initials: M
authors.lastname: Khullar
authors.forename: Indu
authors.initials: I
authors.lastname: Verma
authors.forename: Akshay
authors.initials: A
authors.lastname: Anand
mesh_terms: D002391:Catchment Area, Health; D017931:DNA Primers / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000473:pathology; D020734:Parkinsonian Disorders / Q000453:epidemiology* / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012307:Risk Factors; D013378:Substantia Nigra / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D017931:DNA Primers; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D004298:Dopamine