scholarly journals Functional analysis of the F337C mutation in the CLCN1 gene associated with dominant myotonia congenita reveals an alteration of the macroscopic conductance and voltage dependence

2021 ◽  
Author(s):  
Kevin Jehasse ◽  
Kathleen Jacquerie ◽  
Alice de Froidmont ◽  
Camille Lemoine ◽  
Thierry Grisar ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Voltage Dependence ◽  
Myotonia Congenita ◽  
Clcn1 Gene

scholarly journals Recessive myotonia congenita caused by a homozygous splice site variant in CLCN1 gene: a case report

2020 ◽  
Vol 21 (S1) ◽  
Author(s):  
Peter Sparber ◽  
Margarita Sharova ◽  
Alexandra Filatova ◽  
Olga Shchagina ◽  
Evgeniya Ivanova ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Splice Site ◽  
Muscle Relaxation ◽  
Neuromuscular Disorders ◽  
Voluntary Contraction ◽  
Muscle Stiffness ◽  
Loss Of Function ◽  
Myotonia Congenita ◽  
Clcn1 Gene ◽  
Splice Site Variant

Abstract Background Myotonia congenita is a rare neuromuscular disease, which is characterized by a delay in muscle relaxation after evoked or voluntary contraction. Myotonia congenita can be inherited in a dominant (Thomsen disease) and recessive form (Becker disease) and both are caused by pathogenic variants in the CLCN1 gene. Noncanonical splice site variants are often classified as variants of uncertain significance, due to insufficient accuracy of splice-predicting tools. Functional analysis using minigene plasmids is widely used in such cases. Moreover, functional analysis is very useful in investigation of the disease pathogenesis, which is necessary for development of future therapeutic approaches. To our knowledge only one noncanonical splice site variant in the CLCN1 gene was functionally characterized to date. We further contribute to this field by evaluation the molecular mechanism of splicing alteration caused by the c.1582 + 5G > A in a homozygous state. Case presentation We report a clinical case of an affected 6-y.o boy with athletic appearance due to muscle hypertrophy, calf muscle stiffness, cramping and various myotonic signs in a consanguineous family with no history of neuromuscular disorders. The neurological examination showed percussion-activated myotonia in the hands and legs. Plasma creatine kinase enzyme and transaminases levels were normal. Electromyography at the time of examination shows myotonic runs in the upper and lower extremities. Conclusions Functional analysis of the variant in a minigene system showed alteration of splicing leading to loss of function, thereby confirming that the variant is pathogenic.

Association of Three Different Mutations in the CLCN1 Gene Modulating the Phenotype in a Consanguineous Family with Myotonia Congenita

2021 ◽  
Author(s):  
Lucas Santos Souza ◽  
Priscila Calyjur ◽  
Antonio Fernando Ribeiro ◽  
Juliana Gurgel-Giannetti ◽  
Rita Cassia Mingroni Pavanello ◽  
...  
Keyword(s):  
Consanguineous Family ◽  
Myotonia Congenita ◽  
Clcn1 Gene

scholarly journals ClC-1 Chloride Channel Mutations in Myotonia Congenita: Variable Penetrance of Mutations Shifting the Voltage Dependence

1998 ◽  
Vol 7 (11) ◽  
pp. 1753-1760 ◽  
Author(s):  
C. Kubisch ◽  
T. Schmidt-Rose ◽  
B. Fontaine ◽  
A. H. Bretag ◽  
T. J. Jentsch
Keyword(s):  
Chloride Channel ◽  
Voltage Dependence ◽  
Myotonia Congenita ◽  
Variable Penetrance

scholarly journals Mutations in dominant human myotonia congenita drastically alter the voltage dependence of the CIC-1 chloride channel

Neuron ◽  
1995 ◽  
Vol 15 (6) ◽  
pp. 1455-1463 ◽  
Author(s):  
Michael Pusch ◽  
Klaus Steinmeyer ◽  
Manuela C. Koch ◽  
Thomas J. Jentsch
Keyword(s):  
Chloride Channel ◽  
Voltage Dependence ◽  
Myotonia Congenita

41. Novel mutation in the CLCN1 gene causing myotonia congenita (Thomsen’s disease)

2009 ◽  
Vol 16 (11) ◽  
pp. 1539
Author(s):  
Kishore Kumar ◽  
Karl Ng ◽  
Himesha Vandebona ◽  
Nigel Laing ◽  
Carolyn Sue
Keyword(s):  
Novel Mutation ◽  
Myotonia Congenita ◽  
Clcn1 Gene ◽  
Thomsen's Disease ◽  
Thomsen’S Disease

G.P.14.08 Analysis of the CLCN1 gene in Czech patients with myotonia congenita

2009 ◽  
Vol 19 (8-9) ◽  
pp. 645
Author(s):  
J. Sedlackova ◽  
S. Vohanka ◽  
M. Hermanova ◽  
P. Vondracek ◽  
L. Fajkusova
Keyword(s):  
Myotonia Congenita ◽  
Clcn1 Gene

scholarly journals Role of physiological ClC-1 Cl− ion channel regulation for the excitability and function of working skeletal muscle

2016 ◽  
Vol 147 (4) ◽  
pp. 291-308 ◽  
Author(s):  
Thomas Holm Pedersen ◽  
Anders Riisager ◽  
Frank Vincenzo de Paoli ◽  
Tsung-Yu Chen ◽  
Ole Bækgaard Nielsen
Keyword(s):  
Skeletal Muscle ◽  
Muscle Activity ◽  
Muscle Fibers ◽  
Membrane Conductance ◽  
Membrane Properties ◽  
Equilibrium Potential ◽  
Myotonia Congenita ◽  
Clcn1 Gene ◽  
Wide Range ◽  
Muscle Excitability

Electrical membrane properties of skeletal muscle fibers have been thoroughly studied over the last five to six decades. This has shown that muscle fibers from a wide range of species, including fish, amphibians, reptiles, birds, and mammals, are all characterized by high resting membrane permeability for Cl− ions. Thus, in resting human muscle, ClC-1 Cl− ion channels account for ∼80% of the membrane conductance, and because active Cl− transport is limited in muscle fibers, the equilibrium potential for Cl− lies close to the resting membrane potential. These conditions—high membrane conductance and passive distribution—enable ClC-1 to conduct membrane current that inhibits muscle excitability. This depressing effect of ClC-1 current on muscle excitability has mostly been associated with skeletal muscle hyperexcitability in myotonia congenita, which arises from loss-of-function mutations in the CLCN1 gene. However, given that ClC-1 must be drastically inhibited (∼80%) before myotonia develops, more recent studies have explored whether acute and more subtle ClC-1 regulation contributes to controlling the excitability of working muscle. Methods were developed to measure ClC-1 function with subsecond temporal resolution in action potential firing muscle fibers. These and other techniques have revealed that ClC-1 function is controlled by multiple cellular signals during muscle activity. Thus, onset of muscle activity triggers ClC-1 inhibition via protein kinase C, intracellular acidosis, and lactate ions. This inhibition is important for preserving excitability of working muscle in the face of activity-induced elevation of extracellular K+ and accumulating inactivation of voltage-gated sodium channels. Furthermore, during prolonged activity, a marked ClC-1 activation can develop that compromises muscle excitability. Data from ClC-1 expression systems suggest that this ClC-1 activation may arise from loss of regulation by adenosine nucleotides and/or oxidation. The present review summarizes the current knowledge of the physiological factors that control ClC-1 function in active muscle.

scholarly journals Difference in allelic expression of the CLCN1 gene and the possible influence on the myotonia congenita phenotype

2004 ◽  
Vol 12 (9) ◽  
pp. 738-743 ◽  
Author(s):  
Morten Dunø ◽  
Eskild Colding-Jørgensen ◽  
Morten Grunnet ◽  
Thomas Jespersen ◽  
John Vissing ◽  
...  
Keyword(s):  
Allelic Expression ◽  
Myotonia Congenita ◽  
Clcn1 Gene

scholarly journals Clinical and molecular diagnosis of a Costa Rican family with autosomal recessive myotonia congenita (Becker disease) carrying a new mutation in the CLCN1 gene

2006 ◽  
Vol 56 (1) ◽  
Author(s):  
Fernando Morales ◽  
Patricia Cuenca ◽  
Gerardo Del Valle ◽  
Melissa Vásquez ◽  
Roberto Brian ◽  
...  
Keyword(s):  
Molecular Diagnosis ◽  
Autosomal Recessive ◽  
Costa Rican ◽  
New Mutation ◽  
Myotonia Congenita ◽  
Clcn1 Gene
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