Frequency of the DYT1 mutation in primary torsion dystonia without family history

Arch Neurol. 2000 Mar;57(3):333-5. doi: 10.1001/archneur.57.3.333.

Abstract

Background: Idiopathic torsion dystonia is a clinically and genetically heterogeneous movement disorder. A GAG deletion at position 946 of the DYT1 gene was the first mutation found, in early-onset dystonia, with an autosomal dominant transmission and reduced penetrance.

Objective: To evaluate the frequency of the DYT1 mutation in patients with idiopathic torsion dystonia but without a family history.

Design: Prospective cohort study.

Setting: Four botulinum toxin clinics in the Paris, France, area.

Patients: A French population of 100 patients with dystonia.

Main outcome: Frequency of the DYT1 mutation tested by polymerase chain reaction and enzyme restriction analysis for the 946 GAG deletion, and genotype-to-phenotype correlation.

Results: Only 5 mutation carriers were identified, 4 of whom were part of a group of 10 patients with generalized dystonia. Onset was between ages 5 and 12 years as in typical early-onset dystonia. All 4 patients had cranial muscle involvement, which is atypical for DYT1 mutation carriers. One had segmental dystonia. Molecular analysis of relatives in 2 families demonstrated that the lack of family history was due to reduced penetrance.

Conclusions: For accurate diagnosis and genetic counseling, screening for the DYT1 deletion is of great interest in cases with generalized dystonia without a family history. In other cases, positive results are rare.

MeSH terms

  • Adult
  • Carrier Proteins / genetics*
  • Cohort Studies
  • DNA Mutational Analysis
  • Dystonia Musculorum Deformans / genetics*
  • Female
  • France
  • Genetic Counseling
  • Genetic Testing*
  • Humans
  • Male
  • Middle Aged
  • Molecular Chaperones*
  • Pedigree
  • Prospective Studies

Substances

  • Carrier Proteins
  • Molecular Chaperones
  • TOR1A protein, human