Mapping of a familial essential tremor gene, FET1, to chromosome 3q13

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Abstract

Essential tremor (ET), the most common movement disorder in humans, appears to be inherited as an autosomal dominant trait in many families1,2. The familial form is called familial essential tremor (FET), which seems similar to sporadic essential tremor. ET is a cause of substantial disability, particularly in the elderly1. The prevalence of Parkinson's disease and dystonia may be increased in families with ET, but other movement disorders are seldom encountered in these families3,4. Here we report the results of a genome-wide scan for FET genes in 16 Icelandic families with 75 affected individuals, in whom FET was apparently inherited as a dominant trait. The scan, which was performed with a 10-cM framework map, revealed one locus on chromosome 3q13 to which FET mapped with a genome-wide significance when the data were analysed either parametrically, assuming an autosomal dominant model (lod score = 3.71), or non-parametrically (NPL Z score=4.70, P<6.4×10−6

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References

  1. 1

    Bain, P.G. et al. A study of hereditary essential tremor. Brain 117, 805–824 (1994).

  2. 2

    Koller, W.C., Busenbark, K., Gray, C., Hassanein, R.S & Dubinsky, R. Classification of essential tremor. Clin. Neuropharmacol. 15, 81–87 (1992).

  3. 3

    Koller, W.C., Busenbark, K., Miner, K. & the Essential Tremor Study Group The relationship of essential tremor to other movement disorders: report on 678 patients. Ann. Neurol. 35, 717–723 (1994).

  4. 4

    Jankovic, J., Beach, J., Schwartz, K. & Constant, C. Tremor and longevity in relatives of patients with Parkinson's disease, essential tremor, and control subjects. Neurology 45, 645–648 (1995).

  5. 5

    Salemi, G. et al. Prevalence of essential tremor: a door to door survey in Terrasini, Sicily. Neurology 44, 61–64 (1994).

  6. 6

    Louis, E.D. et al. Differences in the prevalence of essential tremor among elderly African-Americans, whites, and Hispanics in northern Manhattan, NY. Arch. Neurol. 52, 1201–1205 (1995).

  7. 7

    Lou, J.-S. & Jankovic, J. Essential tremor: clinical correlates in 350 patients. Neurology 41, 234–238 (1991).

  8. 8

    Busenbark, K.L., Nash, J., Nash, S., Hubble, J.P. & Koller, W.C. Is essential tremor benign? Neurology 41, 1982–1983 (1991).

  9. 9

    Koller, W.C. & Vetere-Overfield, B. Acute and chronic effects of propranolol and primidone in essential tremor. Neurology 39, 1587–1588 (1989).

  10. 10

    Sasso, E., Perucca, E., Fava, R. & Calzetti, S. Primidone in the long-term treatment of essential tremor: a prospective study with computerized quantitative analysis. Clin. Neuropharmacol. 13, 67–76 (1990).

  11. 11

    Herskovitz, E. & Blackwood, W. Essential tremor: a case report. J. Neurol. Neurosurg. Psychiatry 32, 509–511 (1969).

  12. 12

    Rajput, A.H., Offord, K.P., Beard, C.M. & Kurland, L.T. Essential tremor in Rochester, Minnesota: a 45 year study. J. Neurol. Neurosurg. Psychiatry 47, 466–470 (1984).

  13. 13

    Jenkins, I.H. et al. A positron emission tomography study of essential tremor: evidence for overactivity of cerebellar connections. Ann. Neurol. 34, 82–90 (1993).

  14. 14

    Wills, A.J. et al. Red nuclear and cerebellar but no olivary activation associated with essential tremor: a positron emission tomographic study. Ann. Neurol. 36, 636–642 (1994).

  15. 15

    Boecker, H. et al. The effect of ethanol on alcohol-responsive essential tremor: a positron emission tomography study. Ann. Neurol. 39, 650–658 (1996).

  16. 16

    Im, J.H., Kim, J.S. & Lee, M.C. Disappearance of essential tremor after a small thalamic hemorrhage. Clin. Neurol. Neurosurg. 98, 40–42 (1996).

  17. 17

    Britton, T.C. et al. Rapid wrist movements in patients with essential tremor: the critical role of the second agonist burst. Brain 117, 39–47 (1994).

  18. 18

    Louis, E.D.&, Ottman, R. How familial is familial tremor?The genetic epidemiology of essential tremor. Neurology 46, 1200–1205 (1996).

  19. 19

    Critchley, M. Observations on essential (heredofamilial) tremor. Brain 72, 113–139 (1949).

  20. 20

    Dürr, A. et al. Familial essential tremor and idiopathic torsion dystonia are different genetic entities. Neurology 43, 2212–2214 (1993).

  21. 21

    Jankovic, J., Beach, J., Pandolfo, M. & Patel, P.I. Familial essential tremor in four kindreds. Arch. Neurol. 54,, 289–294 (1997).

  22. 22

    Conway, D. et al. Linkage analysis with chromosome 9 markers in hereditary essential tremor. Mov. Disord. 8, 374–376 (1993).

  23. 23

    Findley, L.J. & Koller, W.C. Definitions and behavioral classifications, in Handbook of Tremor Disorders. (eds Findley, L J. & Koller, W.C.) 1–5 (Dekker, New York, 1994).

  24. 24

    Kruglyak, L., Daly, M.J., Reeve-Daly, M.P. & Lander, E.S. Parametric and nonparametric analysis: a unified multipoint approach. Am. J. Hum. Genet. 58, 1347–1363 (1996).

  25. 25

    Lander, E. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241–247 (1995).

  26. 26

    Baloh, R.W., Foster, C.A., Yue, Q. & Nelson, S.F. Familial migraine with vertigo and essential tremor. Neurology 46, 458–460 (1996).

  27. 27

    Bain, P.G. etal. Assessing tremor severity. J. Neurol. Neurosurg. Psychiatry 56, 868–873 (1993).

  28. 28

    Bain, P.G., Mally, J., Gresty, M. & Findley, L.J. Assessing the impact of essential tremor on upper limb function. J. Neurol. 24, 54–61 (1993).

  29. 29

    Dib, C. et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 380, 152–154 (1996).

  30. 30

    Whittemore, A.S. & Halpern, J. A class of tests for linkage using affected pedigree members. Biometrics 50, 118–127 (1994).

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Correspondence to Kári Stefánsson.

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