title: [Molecular genetic analysis of essential tremor].
abstract: Essential tremor (ET) is the most common extrapyramidal disorder of the central nervous system with autosomal dominant transmission in the majority of cases and age-dependent penetrance of the mutant gene. In a number of cases, it shares some phenotypic features with autosomal dominant idiopathic torsion dystonia (locus DYT1 on chromosome 9q32-34) and is genetically heterogeneous: distinct variants of ET were mapped to chromosomes 3q13 (ETM1) and 2p22-25 (ETM2). We performed studies of candidate loci in a group of Slavonic (11 patients) and Tajik (19 patients) families with ET. Mutational analysis of the DYT gene in probands did not reveal the major deletion 946-948delGAG characteristic of idiopathic torsion dystonia, which allows one to genetically distinguish the studied hereditary forms of ET and torsion dystonia. Based on analysis of genetic linkage in informative Tajik pedigrees with ET, linkage to locus ETM1 on chromosome 3q13 was established in four families. Maximum pairwise Lod score was 2.46 at recombination fraction of theta = 0.00; maximum combined multipoint Lod score was 3.35 for marker D3S3720 and a common "mutant" haplotype for markers D3S3620, D3S3576, and D3S3720 allowed us to locate a mutant gene in a relatively narrow chromosome region spanning 2 cM. In one informative pedigree with ET, both candidate loci ETM1 and ETM2 were definitely excluded on the basis of negative Lod scores obtained by linkage estimations, which testifies to the existence of another distinct gene for autosomal dominant ET.
authors.affiliation: Research Institute of Neurology, Russian Academy of Medical Sciences, Moscow, 125367 Russia. s-illario@mtu-net.ru
authors.forename: S N
authors.initials: SN
authors.lastname: Illarioshkin
authors.forename: R A
authors.initials: RA
authors.lastname: Rakhmonov
authors.forename: I A
authors.initials: IA
authors.lastname: Ivanova-Smolenskaia
authors.forename: A
authors.initials: A
authors.lastname: Brice
authors.forename: E D
authors.initials: ED
authors.lastname: Markova
authors.forename: N I
authors.initials: NI
authors.lastname: Miklina
authors.forename: S A
authors.initials: SA
authors.lastname: Kliushnikov
authors.forename: S A
authors.initials: SA
authors.lastname: Limborskaia
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D002889:Chromosomes, Human, Pair 2; D002893:Chromosomes, Human, Pair 3; D020329:Essential Tremor / Q000208:ethnology / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D018832:Molecular Chaperones; D009154:Mutation; D010375:Pedigree; D012426:Russia; D013620:Tajikistan
chemical_list: D002352:Carrier Proteins; D018832:Molecular Chaperones; C108175:TOR1A protein, human