Myoclonus-dystonia: clinical and genetic evaluation of a large cohort

J Neurol Neurosurg Psychiatry. 2009 Jun;80(6):653-8. doi: 10.1136/jnnp.2008.162099. Epub 2008 Dec 9.

Abstract

Background: Myoclonus-dystonia (M-D) is an autosomal dominant inherited movement disorder. Various mutations within the epsilon-sarcoglycan (SGCE) gene have been associated with M-D, but mutations are detected in only about 30% of patients. The lack of stringent clinical inclusion criteria and limitations of mutation screens by direct sequencing might explain this observation.

Methods: Eighty-six M-D index patients from the Dutch national referral centre for M-D underwent neurological examination and were classified according to previously published criteria into definite, probable and possible M-D. Sequence analysis of the SGCE gene and screening for copy number variations were performed. In addition, screening was carried out for the 3 bp deletion in exon 5 of the DYT1 gene.

Results: Based on clinical examination, 24 definite, 23 probable and 39 possible M-D patients were detected. Thirteen of the 86 M-D index patients carried a SGCE mutation: seven nonsense mutations, two splice site mutations, three missense mutations (two within one patient) and one multiexonic deletion. In the definite M-D group, 50% carried an SGCE mutation and one single patient in the probable group (4%). One possible M-D patient showed a 4 bp deletion in the DYT1 gene (c.934_937delAGAG).

Conclusions: Mutation carriers were mainly identified in the definite M-D group. However, in half of definite M-D cases, no mutation could be identified. Copy-number variations did not play a major role in the large cohort.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Base Pairing / genetics
  • Chromosome Aberrations*
  • Chromosome Deletion
  • Cohort Studies
  • Dystonia / classification
  • Dystonia / diagnosis
  • Dystonia / genetics*
  • Exons / genetics
  • Female
  • Gene Dosage / genetics
  • Genes, Dominant / genetics*
  • Genetic Carrier Screening
  • Genetic Testing
  • Humans
  • Male
  • Middle Aged
  • Molecular Chaperones / genetics*
  • Myoclonus / classification
  • Myoclonus / diagnosis
  • Myoclonus / genetics*
  • Neurologic Examination
  • Sarcoglycans / genetics*
  • Sequence Analysis, DNA
  • Young Adult

Substances

  • Molecular Chaperones
  • SGCE protein, human
  • Sarcoglycans
  • TOR1A protein, human