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

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