The cause of increased excitability in autosomal dominant myotonia congenita (MyC) was studied in resealed greater than 3-cm long segments of muscle fibres from eight patients. Three hours after biopsy only about 50% of the fibre segments had regained a normal resting potential. This differs from our experiences with normal muscle or other disorders of myotonia (e.g. recessive generalized myoto...

Clinical, electrophysiological, and molecular findings are reported for a family with dominant myotonia congenita in which all affected members have experienced long-term fluctuations of the symptom of myotonia. In some patients myotonia is combined with myalgia. The myotonia-causing mutation in this family is in the gene encoding the muscular chloride channel, hCIC-1, predicting the amino acid...

Recessive myotonia congenita (Becker) is genetically linked to HUMCLC, the gene encoding the muscular chloride channel, localized on chromosome 7q35. Three point mutations have so far been reported in HUMCLC, one causing recessive Becker-type myotonia, the others causing the clinically similar Thomsen-type myotonia, which is inherited as a dominant trait. We report a homozygous patient having a...

The muscle Cl- channel, ClC-1, is a member of the ClC family of voltage-gated Cl- channels. Mutations in CLCN1, the gene encoding this channel, cause two forms of inherited human muscle disorders: recessive generalized myotonia congenita (Becker) and dominant myotonia (Thomsen). The functional characterization of these naturally occurring mutations not only allowed a better understanding of the...

Myotonia is repetitive firing of muscle action potentials causing prolonged muscle contractions even after mechanical stimulations to the muscles have ceased. Most common myotonic disorder is myotonic dystrophy which is now termed DM1, myotonic dystrophy type 1. In Japan, proximal myotonic myopathy, which is now called DM2 has not been reported. Both DM1 and DM2 have Cl channel abnormality whic...

Myotonia congenita is caused by mutation of the CLCN1 gene, which encodes the human skeletal muscle chloride channel (ClC-1). The ClC-1 protein is a dimer comprised of two identical subunits each incorporating its own separate pore. However, the precise pathophysiological mechanism underlying the abnormal ClC-1 channel gating in some mutants is not fully understood. We characterized a ClC-1 mut...

The myotonic disorders are a heterogeneous group of genetically determined diseases that are unified by the presence of myotonia, which is defined as failure of muscle relaxation after activation. The presentation of these disorders can range from asymptomatic electrical myotonia, as seen in some forms of myotonia congenita (MC), to severe disability with muscle weakness, cardiac conduction def...