The Movement Disorders Division studies the genetic and environmental risk factors for a variety of degenerative diseases including Parkinson's disease (PD), essential tremor, and Huntington's disease. Several clinical trials and observational studies are ongoing.
Drs. Karen Marder, Lorraine Clark, and colleagues have examined several newly identified mutations associated in a unique sample of Parkinson's disease patients, half of whom were recruited because their symptoms began at or before the age of 50 (early onset) and half after 50 (late onset), and controls recruited by random digit dialing. We completely sequenced the parkin gene and looked for exon deletions and duplications. We found that 9.9 percent of 101 early-onset PD cases had mutations in the parkin gene, which is comparable to other studies of early-onset PD patients who do not report a family history of PD. Importantly, because of the ethnic diversity in our sample, we also showed that the frequency of a previously identified mutation (Leu261Leu) was similar in cases and controls, suggesting that this is not, in fact, a mutation. This study demonstrates the importance of examining purported mutations in various ethnic groups.
Dr. Louis and colleagues have linked several environmental toxins with essential tremor (ET). Harmane is a highly tremorogenic toxin, and work by Dr. Louis and colleagues suggests that a metabolic defect may be responsible for the elevated blood harmane concentration that has been observed in ET cases. Further work on dietary and genetic differences between ET cases and controls will examine the role that these factors play in explaining the link between these toxins and ET.
Dr. Louis and colleagues recently established the Essential Tremor Centralized Brain Repository at Columbia University. They have identified pathological material on thirty-one ET cases, finding an identifiable pathology in ET. Cases of ET seem to cluster into two groups: cases with mild cerebellar degenerative changes versus those with a focal presence of Lewy bodies in the locus ceruleus. These studies show that pathological changes are indeed identifiable, that the disease is likely to be a pathologically heterogeneous family of diseases, and that there is a link between ET and Lewy body disease.