Neuroscience Letters 376 (2005) 56–59 Analysis of the trinucleotide CAG repeat from the DNA polymerase  gene (POLG) in patients with Parkinson’s disease Jan-Willem Taanman a,∗ , Anthony H.V. Schapira a,b a University Department of Clinical Neurosciences, Royal Free and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK b Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK Received 5 August 2004; received in revised form 6 November 2004; accepted 11 November 2004 Abstract The human gene for the catalytic subunit of the mitochondrial DNA (mtDNA) polymerase (POLG) contains a trinucleotide CAG repeat encoding a polyglutamine tract near the amino-terminus of the protein. Expansions of similar polyglutamine-encoding CAG microsatellite repeats in other genes are known to cause neurodegenerative disorders. As mitochondrial dysfunction has been implicated in the aetiology of Parkinson’s disease, we determined the POLG CAG repeat length in DNA samples extracted from 22 idiopathic Parkinson’s disease patients and 31 control subjects. The distribution of the POLG CAG repeat length in the control samples matched the distribution reported for control samples by others. Comparison between the CAG repeat length distribution of control and Parkinson’s disease samples revealed no evidence of either germ line or somatic POLG CAG repeat instability in Parkinson’s disease patients. Our results rule out POLG CAG repeat instability as a common pathogenic mechanism in idiopathic Parkinson’s disease. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: DNA polymerase ; POLG; Parkinson’s disease; CAG repeat; Polyglutamine tract; Mitochondria Parkinson’s disease is a neurodegenerative disorder associ- ated with a loss of dopaminergic neurons in the substantia nigra, as well as more widespread neuronal loss in other parts of the brain. A number of genes responsible for rare familial forms of Parkinson’s disease have been identified [4,9,29]. The majority of Parkinson’s disease cases are, however, spo- radic. Although the aetiology of the disease in these sporadic cases remains undefined, it is now widely accepted that ge- netic susceptibility factors exist that may interact with envi- ronmental factors and result in the development of Parkin- son’s disease. Several lines of evidence have implicated mitochondrial dysfunction in the pathogenesis of Parkinson’s disease. De- ficiency of the mitochondrial respiratory chain enzyme com- plex I has been found in post-mortem brains of Parkinson’s ∗ Corresponding author. Tel.: +44 20 77940500x5354; fax: +44 20 74726829. E-mail address: j.taanman@rfc.ucl.ac.uk (J.-W. Taanman). disease patients [13,24]. In addition, the environmental tox- ins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and annonacin appear to induce relatively selective death of dopaminergic neurons through inhibition of complex I [2,7,19]. Indirect evidence suggests that the mitochondrial dysfunction in some Parkinson’s disease patients may be due to mutations in mitochondrial DNA (mtDNA). Seven of the 13 protein genes of mtDNA code for subunits of com- plex I [27]. Therefore, complex I is particularly vulnera- ble to mtDNA mutations. Cybrids containing mtDNA from platelets of sporadic Parkinson’s disease patients showed de- creased complex I activity [12,26], indicating a mtDNA trans- mission of the mitochondrial defect in these patients. Fur- thermore, Parkinsonism has been reported in sporadic and familial cases presenting with progressive external ophthal- moplegia and multiple deletions of mtDNA [5,6,8,10,18,31]. Three genes, all coding for mitochondrial proteins, are known to cause familial progressive external ophthalmoplegia with multiple mtDNA deletions: the gene for adenine nucleotide 0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.11.023