Essential Tremor (ET) is a heterogenous tremor disorder characterized by a core group of features. The tremor syndrome is characterized by postural and kinetic tremor affecting the arms and hands, although the head, voice, and legs may also be affected. Although frequently described as a benign disorder, this is not true; many patients are socially and physically handicapped, with some patients being totally disabled. The differential diagnosis list for ET is extensive including dystonia, Parkinsonism, myoclonus, peripheral neuropathy, and other conditions. Prevalence estimates range widely, depending upon methodology and diagnostic criteria, from 0.003 to as high as 2% in the general population, with as much as 5% of the population affected over the age of 65. There are no known biological or diagnostic neuropathological markers for ET. The estimates of ET cases presenting with a positive family history range from 17.4% to 100%. Recent studies indicate that up to 96% of ET may be dominantly inherited. Clinical and genetic heterogeneity have slowed linkage studies. To date three loci associated with ET have been linked: 1) Familial Essential Tremor 1 (FET1) has been mapped in a series of Icelandic families on chromosome 3q13; (2) ETM mapped, in four unrelated US families, to chromosome 2p22-p25; and (3) a third locus maps, in a family that segregates both Parkinson's disease and postural tremor consistent with ET, to Chromosome 4p. We have, to date, ascertained, twelve ET and ET/PD linkage quality families. The largest pure ET kindred (DUK13001) have been excluded from known ET loci.
The aims of this proposal are to ascertain and sample large families with ET, carry out a complete ET genome scan to establish linkage for these and additional ET families, identify new ET disease loci, and isolate and characterize ET genes, beginning with DUK13001 ET family.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS043473-02
Application #
6623588
Study Section
Special Emphasis Panel (ZRG1-EDC-3 (01))
Program Officer
Oliver, Eugene J
Project Start
2002-03-15
Project End
2006-02-28
Budget Start
2003-03-01
Budget End
2004-02-29
Support Year
2
Fiscal Year
2003
Total Cost
$365,750
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Hicks, James E; Konidari, Ioanna; Scott, Burton L et al. (2016) Linkage of familial essential tremor to chromosome 5q35. Mov Disord 31:1059-62