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J Med Genet 38:e35 doi:10.1136/jmg.38.10.e35
  • Electronic letter

No evidence of allelic heterogeneity in theDYT1 gene of European patients with early onset torsion dystonia

  1. Sylvie Tuffery-Girauda,
  2. Laurent Cavaliera,
  3. Agathe Roubertieb,
  4. Caroline Guittarda,
  5. Soukeyna Carlesa,
  6. Patrick Calvasc,
  7. Bernard Echenneb,
  8. Philippe Coubesd,
  9. Mireille Claustresa
  1. aLaboratory of Molecular Genetics, CHU Montpellier, France, bPaediatric Neurology, Saint Eloi Hospital, Montpellier, France, cLaboratory of Medical Genetics, Purpan Hospital, Toulouse, France, dPaediatric Neurosurgery, Gui de Chauliac Hospital, Montpellier, France
  1. Dr Tuffery-Giraud, Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique (IURC), 641 avenue du Doyen Gaston Giraud, 34093 Montpellier Cedex 5, France, tuffery{at}igh.cnrs.fr

    Editor—Torsion dystonia is a movement disorder characterised by sustained involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal postures.1 Primary torsion dystonia (PTD) occurs either in a familial or sporadic pattern with dystonia as the sole phenotypic manifestation with the exception that tremor can be present as well. Early onset, generalised torsion dystonia is the most severe form of hereditary dystonia, and the most prevalent form is the result of mutation in the DYT1(TOR1A) gene on chromosome 9q34.2 Inheritance follows an autosomal dominant mode of transmission with reduced penetrance (30-40%),3 and there is a particularly high prevalence in Ashkenazi Jews (AJ) as a result of a founder effect and genetic drift.4 Early onset primary dystonia resulting from DYT1 usually starts in an arm or a leg at a mean age of 12.5 years (this can range, however, from 4 to 44 years).5 More than 60-70% of cases have progression to generalised dystonia involving limb and axial muscles, but the cranial muscles are only involved in 11-18% of cases.6 The causative mutation has been identified as a 3 bp deletion (946delGAG) in the coding sequence of theDYT1 gene, resulting in loss of one of a pair of glutamic acid residues near the C-terminus of the encoded protein, torsinA.7 Presumably, deletion of this amino acid results in a critical change in the function of the gene product that leads to clinical signs of dystonia.

    Currently, this mutation is the only sequence change found to be associated with the disease state, regardless of ethnic origin, both as an inherited7 or a de novo deletion.8 The ΔGAG in the heterozygous state accounts for 50-60% of non-Jewish (NJ) subjects9-11 and over 90% of AJ subjects5 with early, limb …