title: Frequency and phenotypic variability of the GAG deletion of the DYT1 gene in an unselected group of patients with dystonia.
abstract: BACKGROUND
  Dystonia is a clinically and genetically heterogeneous movement disorder characterized by sustained muscle contractions affecting one or more sites of the body, frequently causing twisting and repetitive movements or abnormal postures. A 3-base pair (GAG) deletion in the DYT1 gene is held responsible for most cases of early-onset primary generalized dystonia in the Ashkenazi Jewish population as well as in non-Jewish patients.
  
  
  OBJECTIVE
  To investigate the prevalence of the GAG deletion in the DYT1 gene and the phenotypic variability in the general population by testing patients with different subtypes of dystonia from 4 different movement disorder outpatient clinics in Germany.
  
  
  METHODS
  Two hundred fifty-six patients were tested for the GAG deletion mutation in the DYT1 gene by means of published primers and polymerase chain reaction amplification to determine GAG deletion status.
  
  
  RESULTS
  Six of the 256 patients did carry the GAG-deletion in the DYT1 gene. However, only 2 of the 6 mutation carriers presented with what is thought to represent classic features of early-onset primary generalized dystonia. The DYT1 mutation was also detected in 2 patients with multifocal dystonia, 1 of them presenting with involvement of cranial and cervical muscles, and in 2 patients with writer's cramp of both hands with only slight progression. Our findings demonstrate that the mutation may be associated with not only generalized but also segmental and multifocal forms of dystonia.
  
  
  CONCLUSIONS
  Our data underline the wide range of phenotypic variability of the DYT1 mutation. A priori prediction of the mutation carrier status in dystonic patients and genetic counseling of affected families with respect to the clinical manifestation may prove difficult.
authors.affiliation: Department of Neurology, University of Tübingen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Grundmann
authors.forename: Ulrike
authors.initials: U
authors.lastname: Laubis-Herrmann
authors.forename: Ingrid
authors.initials: I
authors.lastname: Bauer
authors.forename: Dirk
authors.initials: D
authors.lastname: Dressler
authors.forename: Juliane
authors.initials: J
authors.lastname: Vollmer-Haase
authors.forename: Peter
authors.initials: P
authors.lastname: Bauer
authors.forename: Manfred
authors.initials: M
authors.lastname: Stuhrmann
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schulte
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
authors.forename: Helge
authors.initials: H
authors.lastname: Topka
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
mesh_terms: D020029:Base Pairing / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004421:Dystonia / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D014644:Genetic Variation; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D011187:Posture; D015995:Prevalence
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D018832:Molecular Chaperones; C108175:TOR1A protein, human