title: Myoclonus-dystonia: clinical and genetic evaluation of a large cohort.
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.
authors.affiliation: Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Ritz
authors.forename: M C F
authors.initials: MC
authors.lastname: Gerrits
authors.forename: E M J
authors.initials: EM
authors.lastname: Foncke
authors.forename: F
authors.initials: F
authors.lastname: van Ruissen
authors.forename: C
authors.initials: C
authors.lastname: van der Linden
authors.forename: M D I
authors.initials: MD
authors.lastname: Vergouwen
authors.forename: B R
authors.initials: BR
authors.lastname: Bloem
authors.forename: W
authors.initials: W
authors.lastname: Vandenberghe
authors.forename: R
authors.initials: R
authors.lastname: Crols
authors.forename: J D
authors.initials: JD
authors.lastname: Speelman
authors.forename: F
authors.initials: F
authors.lastname: Baas
authors.forename: M A J
authors.initials: MA
authors.lastname: Tijssen
mesh_terms: D000293:Adolescent; D000328:Adult; D020029:Base Pairing / Q000235:genetics; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D015331:Cohort Studies; D004421:Dystonia / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics*; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics*; D009207:Myoclonus / Q000145:classification / Q000175:diagnosis / Q000235:genetics*; D009460:Neurologic Examination; D049031:Sarcoglycans / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D018832:Molecular Chaperones; C526572:SGCE protein, human; D049031:Sarcoglycans; C108175:TOR1A protein, human