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

Jeffrey R. Gulcher¹, Þorlákur Jónsson¹, Augustine Kong^1, 2, Kristleifur Kristjánsson¹, Michael L. Frigge^1, 2, Ari Kárason¹, Ingibjörg E. Einarsdóttir¹, Hreinn Stefánsson¹, Anna S. Einarsdóttir¹, Sigrún Sigurdardttir¹, Sigurur Baldursson¹, Sóley Björnsdóttir¹, Soffía M. Hrafnkelsdóttir¹, Finnbogi Jakobsson³, John Benedickz^1, 4 & Kári Stefánsson^1, 5

  ¹deCODE Genetics, Lynghals 1,110 Reykjavik, Iceland.

  ²Department of Statistics, University of Chicago, Chicago, Illinois 60637, USA.

  ³Department of Neurology, Reykjavik Hospital, 108 Reykjavik, Iceland.

  ⁴Department of Neurology, National Hospital of Iceland, 101 Reykjavik, Iceland.

  ⁵e-mail: kstefans@decode.is.

Essential tremor (ET), the most common movement disorder in humans, appears to be inherited as an autosomal dominant trait in many families^1,2. 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 families^3,4. 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<6.410^-6

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