A neurophysiological study of myoclonus in patients with DYT11 myoclonus‐dystonia syndrome

Marelli, Cécilia; Canafoglia, Laura; Zibordi, Federica; Ciano, Claudia; Visani, Elisa; Zorzi, Giovanna; Garavaglia, Barbara; Barzaghi, Chiara; Albanese, Alberto; Soliveri, Paola; Leone, Massimo; Panzica, Ferruccio; Scaioli, V.; Pincherle, Alessandro; Nardocci, Nardo; Franceschetti, Silvana

doi:10.1002/mds.22256

Cited by 42 publications

(36 citation statements)

References 37 publications

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“…Furthermore, in MDS the symptoms are clearly ameliorated by alcohol, which was not the case in this family. Additionally, in MDS the myoclonus is of subcortical origin and is not stimulus-sensitive, and giant SSEPs are never observed 10,11 . Finally, in this family we excluded linkage to known MDS chromosomal regions 7,8 , and we sequenced but found no mutations in the SCGE gene 8,9 .…”

Section: Discussionmentioning

confidence: 99%

Familial cortical myoclonus with a mutation in NOL3

Russell

Steckley

Coppola

et al. 2012

Annals of Neurology

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Objective Myoclonus is characterized by sudden, brief involuntary movements and its presence is debilitating. We identified a family suffering from adult-onset, cortical myoclonus without associated seizures. We performed clinical, electrophysiological, and genetic studies to define this phenotype. Methods A large, four-generation family with history of myoclonus underwent careful questioning, examination, and electrophysiological testing. Thirty-five family members donated blood samples for genetic analysis, which included SNP mapping, microsatellite linkage, targeted massively parallel sequencing, and Sanger sequencing. In silico and in vitro experiments were performed to investigate functional significance of the mutation. Results We identified 11 members of a Canadian Mennonite family suffering from adult-onset, slowly progressive, disabling, multifocal myoclonus. Somatosensory evoked potentials indicated a cortical origin of the myoclonus. There were no associated seizures. Some severely affected individuals developed signs of progressive cerebellar ataxia of variable severity late in the course of their illness. The phenotype was inherited in an autosomal dominant fashion. We demonstrated linkage to chromosome 16q21-22.1. We then sequenced all coding sequence in the critical region, identifying only a single co-segregating, novel, nonsynonymous mutation, which resides in the gene NOL3. Furthermore, this mutation was found to alter post-translational modification of NOL3 protein in vitro. Interpretation We propose that Familial Cortical Myoclonus (FCM) is a novel movement disorder that may be caused by mutation in NOL3. Further investigation of the role of NOL3 in neuronal physiology may shed light on neuronal membrane hyperexcitability and pathophysiology of myoclonus and related disorders.

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Section: Discussionmentioning

confidence: 99%

Familial cortical myoclonus with a mutation in NOL3

Russell

Steckley

Coppola

et al. 2012

Annals of Neurology

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“…Electrophysiological studies in man suggest that myoclonic symptoms are of subcortical origin. [1][2][3] In general, dystonia is thought to arise from dysfunction of the basal ganglia. 4 About 50% of M-D patients who were classified as definite M-D carry a mutation in the widely expressed e-sarcoglycan (SGCE).…”

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confidence: 99%

SGCE isoform characterization and expression in human brain: implications for myoclonus–dystonia pathogenesis?

et al. 2010

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Myoclonus-dystonia (M-D) is a neurological movement disorder with involuntary jerky and dystonic movements as major symptoms. About 50% of M-D patients have a mutation in e-sarcoglycan (SGCE), a maternally imprinted gene that is widely expressed. As little is known about SGCE function, one can only speculate about the pathomechanisms of the exclusively neurological phenotype in M-D. We characterized different SGCE isoforms in the human brain using ultra-deep sequencing. We show that a major brain-specific isoform is differentially expressed in the human brain with a notably high expression in the cerebellum, namely in the Purkinje cells and neurons of the dentate nucleus. Its expression was low in the globus pallidus and moderate to low in caudate nucleus, putamen and substantia nigra. Electrophysiological studies in man suggest that myoclonic symptoms are of subcortical origin. [1][2][3] In general, dystonia is thought to arise from dysfunction of the basal ganglia. 4 About 50% of M-D patients who were classified as definite M-D carry a mutation in the widely expressed e-sarcoglycan (SGCE). [5][6][7] The genetic cause in the remaining patients is still unclear. A second locus has been reported in one large M-D family (DYT15, 18p11), but no gene has been identified yet. 8,9 SGCE is part of the sarcoglycan family that consists of N-glycosylated transmembrane proteins. Six different sarcoglycans have been identified so far (a-, b-, g-, d-, e-and z-), but little is known about the function of particular sarcoglycan members and their function in different tissues. 10 In muscles, sarcoglycans form a heterotetrameric complex that is constituent of the dystrophinassociated protein complex. This complex mediates the structural stability of the plasma membrane and interactions between the extracellular matrix and the cytoskeleton. 11 Mutations in other sarcoglycans, a-, b-, g-and d-sarcoglycan, lead to different forms of limb-girdle muscular dystrophy, characterized by progressive muscle weakness. 10 Little is known about composition and function of the dystrophin-associated protein complex in the brain. SGCE is highly homologous to a-sarcoglycan, 12 but no muscle

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“…However in some studies, primary dysfunction of basal ganglions have been implicated in its pathophysiology. Nonobservance of C-reflex, premyoclonic critical discharges, and giant somatosensory evoked potentials on EEG, indicates subcortical origin of myoclonic jerks [3, 11]. Dramatic response obtained with deep brain stimulation (DBS) applied on globus pallidus internus (GPI) in patients with MDS suggests involvement of GPI among subcortical structures [5].…”

Section: Discussionmentioning

confidence: 99%

Myoclonus-dystonia syndrome: case report

Akarsu¹,

Sürmeli

Yalcin

2015

North Clin Istanbul

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Myoclonus-dystonia syndrome (MDS) is a rare disease manifesting myoclonus as the only neurological symptom which may be accompanied by dystonia. It usually starts in the first or second decade of life. It has a benign course with spontaneous remissions but can cause functional disability in some patients. In this paper, we report a patient diagnosed as probable MDS on the basis of clinical and electrophysiological features who showed marked improvement under levetiracetam treatment.

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A neurophysiological study of myoclonus in patients with DYT11 myoclonus‐dystonia syndrome

Cited by 42 publications

References 37 publications

Familial cortical myoclonus with a mutation in NOL3

Familial cortical myoclonus with a mutation in NOL3

SGCE isoform characterization and expression in human brain: implications for myoclonus–dystonia pathogenesis?

Myoclonus-dystonia syndrome: case report

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