Journal Article

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

Foncke, E M J, van Ruissen, F, Vandenberghe, W, Tijssen, M A J, Gerrits, M C F, Bloem, B R, Crols, R, Vergouwen, M D I, van der Linden, C, Ritz, K, Speelman, J D, Baas, F

2009

Overview

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.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group,BMJ Publishing Group LTD
• Subject: Adolescent / Adult / Age / Alcohol / Anxiety / Base Pairing - genetics / Biological and medical sciences / Chromosome Aberrations / Chromosome Deletion / Classification / Cohort Studies / Diseases of striated muscles. Neuromuscular diseases / Dystonia - classification / Dystonia - diagnosis / Dystonia - genetics / Exons - genetics / Fear & phobias / Female / Gene Dosage - genetics / Genes / Genes, Dominant - genetics / Genetic Carrier Screening / Genetic Testing / Genotype & phenotype / Humans / Male / Medical sciences / Middle Aged / Molecular Chaperones - genetics / Mutation / Myoclonus - classification / Myoclonus - diagnosis / Myoclonus - genetics / Neurologic Examination / Neurology / Patients / Proteins / Sarcoglycans - genetics / Sequence Analysis, DNA / Young Adult