Evidence that a gene for essential tremor maps to chromosome 2p in four families (vol 13, pg 972, 1998)

In this Journal, we previously reported genetic linkage between loci on chr omosome (chr) 2p (ETM) and dominantly inherited essential tremor (ET) in a large American kindred of Czech ancestry. Other investigators reported anot her ET susceptibility locus on chr 3q (FET1) which accounted for over half of the Icelandic families that were studied. We now report evidence for lin kage to the ETM locus in three additional, unrelated American families with ET and exclude the FET1 locus in these families. Fine mapping results, usi ng an "affecteds-only" model in all four American families, demonstrate pos itive combined pairwise lad scores (Z) at the ETM locus with a Z(max) = 5.9 4 at a recombination fraction (theta) = 0.00 for locus D2S220. Haplotype re construction places the ETM gene in a 9.10 cM interval between the D2S224 a nd D2S405 loci. Multipoint linkage analysis suggests that the ETM gene is i n the 2.18 cM interval between loci D2S2150 and D2S220 with a Z(max) = 8.12 . These findings may facilitate the search for a gene that causes ET and ma y further our understanding of other disorders that are associated with tre mor.