OBJECTIVE To redefine phenotypical characteristics for both chloride (ClCh) and sodium channelopathies (NaCh) in non-dystrophic myotonic syndromes (NDM). METHODS In a cross-sectional, nationwide study, standardised interviews and clinical bedside tests were performed in 62 genetically confirmed NDM patients, 32 ClCh and 30 NaCh. RESULTS Standardised interviews revealed that ClCh reported a ...

RNA-mediated pathogenesis is a recently developed disease model that proposes that certain types of mutant genes produce toxic transcripts that inhibit the activities of specific proteins. This pathogenesis model was proposed first for the neuromuscular disease myotonic dystrophy (DM), which is associated with the expansion of structurally related (CTG)(n) and (CCTG)(n) microsatellites in two u...

Myotonia congenita is a human muscle disorder caused by mutations in CLCN1, which encodes human chloride channel 1 (CLCN1). Zebrafish is becoming an increasingly useful model for human diseases, including muscle disorders. In this study, we generated transgenic zebrafish expressing, under the control of a muscle specific promoter, human CLCN1 carrying mutations that have been identified in huma...

In myotonic dystrophy (MD), disease severity has been correlated with expansion of CTG repeats in chromosome 19. The aims of this study were to evaluate efficacy of electromyography in the diagnosis of MD, access the frequency and the characteristics of peripheral involvement in the disease and to verify whether the CTG repeats correlated with the electrophysiological abnormalities. Twenty-five...

A point mutation (D136G) predicting the substitution of glycine for aspartate in position 136 of the human muscle Cl- channel (hClC-1) causes recessive generalized myotonia. Heterologous expression of a recombinant D136G produces functional Cl- channels with profound alterations in voltage-dependent gating, without concomitant changes in pore properties. The mutant exhibits slowly activating cu...

The linkages between a protein 's primary sequence, three-dimensional structure, and the detailed manifestations of its function are well appreciated. Exploring and understanding these linkages have proven remarkably complex, however. While some functions may be localized exclusively to one protein region, others may be distributed or even diffusely coded in the structure. The kinetics of the t...