Myoclonus–dystonia: clinical and genetic evaluation of a large cohort
- K Ritz1,2,
- M C F Gerrits3,
- E M J Foncke1,
- F van Ruissen2,
- C van der Linden4,
- M D I Vergouwen1,
- B R Bloem5,
- W Vandenberghe6,
- R Crols7,
- J D Speelman1,
- F Baas2,
- M A J Tijssen1
- 1Department of Neurology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
- 2Neurogenetic Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
- 3Department of Neurology, Bronovo Hospital, The Hague, The Netherlands
- 4Centre for Movement Disorders, St Lucas Hospital Ghent, Ghent, Belgium
- 5Department of Neurology, Radboud University Nijmegen Medical Centre, Donders Centre for Neuroscience, Nijmegen, The Netherlands
- 6Department of Neurology, University Hospital Leuven, Leuven, Belgium
- 7Department of Neurology, Middelheim Hospital, Antwerp, Belgium
- Dr M A J Tijssen, Department of Neurology H2-261, Academic Medical Centre, University of Amsterdam, PO Box 22660, 1100 DD Amsterdam, The Netherlands;
- Received 3 September 2008
- Revised 10 November 2008
- Accepted 12 November 2008
- Published Online First 9 December 2008
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.
Funding: This study has been supported by Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) VIDI (project 016.056.333 to KR and MAJT).
Competing interests: None.
Patient consent: Obtained.