A linkage study of candidate loci in familial Parkinson's Disease

• Main Authors: Westerberg Lisa, Burgess Catherine E, Wirdefeldt Karin, Payami Haydeh, Schalling Martin
• Format: Article
• Language: English
• Published: BMC 2003-07-01
• Series: BMC Neurology
• Online Access: http://www.biomedcentral.com/1471-2377/3/6

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease. Most cases are sporadic, however familial cases do exist. We examined 12 families with familial Parkinson's disease ascertained at the Movement Disorder clinic at the Oregon Health Sciences University for genetic linkage to a number of candidate loci. These loci have been implicated in familial Parkinson's disease or in syndromes with a clinical presentation that overlaps with parkinsonism, as well as potentially in the pathogenesis of the disease.</p> <p>Methods</p> <p>The examined loci were <it>PARK3</it>, <it>Parkin</it>, <it>DRD </it>(dopa-responsive dystonia), <it>FET1 </it>(familial essential tremor), <it>BDNF </it>(brain-derived neurotrophic factor), <it>GDNF </it>(glial cell line-derived neurotrophic factor), <it>Ret</it>, <it>DAT1 </it>(the dopamine transporter), <it>Nurr1 </it>and <it>Synphilin</it>-1. Linkage to the α-<it>synuclein </it>gene and the <it>Frontotemporal dementia with parkinsonism </it>locus on chromosome 17 had previously been excluded in the families included in this study. Using Fastlink, Genehunter and Simwalk both parametric and model-free non-parametric linkage analyses were performed.</p> <p>Results</p> <p>In the multipoint parametric linkage analysis lod scores were below -2 for all loci except <it>FET1 </it>and <it>Synphilin</it>-1 under an autosomal dominant model with incomplete penetrance. Using non-parametric linkage analysis there was no evidence for linkage, although linkage could not be excluded. A few families showed positive parametric and non-parametric lod scores indicating possible genetic heterogeneity between families, although these scores did not reach any degree of statistical significance.</p> <p>Conclusions</p> <p>We conclude that in these families there was no evidence for linkage to any of the loci tested, although we were unable to exclude linkage with both parametric and non-parametric methods.</p>