Disease relevance of Myotonia Congenita

• This is based on analysis of the dominant negative effects of ClC-1 mutations causing myotonia congenita (MC, Thomsen's disease), including a newly identified mutation (P480L) in Thomsen's own family [1].
• Mutations in the gene encoding this chloride channel (CLCN1) are responsible for both human purely myotonic disorders, autosomal recessive generalized myotonia (Becker's disease, GM) and autosomal dominant myotonia congenita (Thomsen's disease, MC) [2].
• Ouabain infusion did not affect the recovery from transient paresis or the accompanying electromyographic changes, indicating that the warming-up phenomenon in generalized myotonia is not mediated by Na(+)-K(+)-ATPase [3].

High impact information on Myotonia Congenita

• We conclude that the Thomsen disease locus is linked to the TCRB locus in these families [4].
• The chromosomal localization of the gene for Thomsen disease, an autosomal dominant form of myotonia congenita, is unknown [4].
• Two-point linkage analysis between Thomsen disease and TCRB showed a maximum cumulative lod score of 3.963 at a recombination fraction of .10 (1-lod support interval .048-.275) [4].
• Linkage of Thomsen disease to the T-cell-receptor beta (TCRB) locus on chromosome 7q35 [4].
• Recent in vitro electrophysiologic studies have demonstrated abnormal sodium channel gating in muscle from patients with Thomsen's disease and have called the chloride hypothesis into question [5].

Chemical compound and disease context of Myotonia Congenita

• In cases reported in the literature where myotonia developed in association with either propranolol (beta-adrenergic blocking agent) or fenoterolhydrobromide (stimulator of beta receptors) heterozygote manifestation of recessive generalized myotonia is suggested [6].
• A young women treated with fenoterol developed severe generalized myotonia [7].
• By sequence analysis, we identified a C-to-A transition at nucleotide position 1438, resulting in a substitution of proline for threonine at amino acid position 480 (P480T), the same position of the original mutation (P480L) in Thomsen's disease [8].
• Clinical and electrophysiological reports in a case of early onset myotonia congenita (Thomsen's disease) successfully treated with mexiletine [9].
• Successful dantrolene sodium treatment of a patient with myotonia congenita (Thomsen's disease) [10].

Biological context of Myotonia Congenita

• Linkage analysis of Thomsen disease to the T-cell-receptor beta (TCRB) locus at 7q35 was carried out in four pedigrees (25 affected and 23 unaffected individuals) by using a PCR-based dinucleotide repeat polymorphism in the TCRB gene [4].

Gene context of Myotonia Congenita

• In 2 controls and in 2 patients with generalized myotonia, as well as in 1 patient with myotonia congenita (where the defect is in chloride channels), apamin had no effect [11].

References