title: Intrafamilial phenotypic and genetic heterogeneity of dystonia.
abstract: Most cases of early-onset primary torsion dystonia are caused by the same 3-bp (GAG) deletion in the DYT1 gene. We describe a large Serbian family with significant intrafamilial variability of the DYT1 phenotype, from asymptomatic carrier status to late-onset focal, and generalized jerky dystonia. Seven mutation carriers (six proven by direct analysis and one by inferred haplotype) were identified, but only two of them were affected by dystonia (penetrance reduced to 29%). In addition, three GAG-deletion-negative family members also developed dystonia (two multifocal dystonia and one torticollis), suggesting that their involuntary movements are due to some other etiological factor(s) (i.e., another dystonia gene), or may be psychogenic.
authors.affiliation: Institute of Neurology CCS, School of Medicine, Ul. Dr Subotića 6, 11000 Belgrade, Serbia and Montenegro. vkostic@sbb.co.yu
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Kostić
authors.forename: Marina
authors.initials: M
authors.lastname: Svetel
authors.forename: Kemal
authors.initials: K
authors.lastname: Kabakci
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Ristić
authors.forename: Igor
authors.initials: I
authors.lastname: Petrović
authors.forename: Birgitt
authors.initials: B
authors.lastname: Schüle
authors.forename: Norman
authors.initials: N
authors.lastname: Kock
authors.forename: Ana
authors.initials: A
authors.lastname: Djarmati
authors.forename: Stanka
authors.initials: S
authors.lastname: Romac
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
mesh_terms: D000328:Adult; D000368:Aged; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D020821:Dystonic Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004777:Environment; D005192:Family Health; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D015022:Yugoslavia
chemical_list: D005819:Genetic Markers; D018832:Molecular Chaperones; C108175:TOR1A protein, human