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Myoclonus-Dystonia: clinical and genetic evaluation of a large cohort
  1. Katja Ritz (k.a.ritz{at}amc.uva.nl)
  1. Academic Medical Centre, Netherlands
    1. Mignon CF Gerrits (mignongerrits{at}hotmail.com)
    1. Bronovo Hospital, Netherlands
      1. Elisabeth MJ Foncke (e.m.foncke{at}amc.uva.nl)
      1. Academic Medical Centre, Netherlands
        1. Fred van Ruissen (f.vanruissen{at}amc.uva.nl)
        1. Academic Medical Centre, Netherlands
          1. Chris van der Linden (secretariaat.vanderlinden{at}azstlucas.be)
          1. St. Lucas Hospital Ghent, Belgium
            1. Mervyn D I Vergouwen (m.d.vergouwen{at}amc.uva.nl)
            1. Academic Medical Centre, Netherlands
              1. Bastiaan R Bloem (b.bloem{at}neuro.umcn.nl)
              1. Radboud University Nijmegen Medical Centre, Netherlands
                1. Wim Vandenberghe (wim.vandenberghe{at}uz.kuleuven.ac.be)
                1. University Hospital Leuven, Belgium
                  1. Roeland Crols (roeland.crols{at}zna.be)
                  1. Middelheim Hospital, Belgium
                    1. Johannes D Speelman (j.d.speelman{at}amc.uva.nl)
                    1. Academic Medical Centre, Netherlands
                      1. Frank Baas (f.baas{at}amc.uva.nl)
                      1. Academic Medical Centre, Netherlands
                        1. Marina A J de Koning-Tijssen (m.a.tijssen{at}amc.uva.nl)
                        1. Academic Medical Centre, Netherlands

                          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 center 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, we screened 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 multi-exonic deletion. In the definite M-D group 50% carried a SGCE mutation and one single patient in the probable group (3%). 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 our large cohort.

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