Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Gene/Protein
Disease
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Drug
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Target Concepts:
Gene/Protein
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Query: UMLS:C0026827 (
hypotonia
)
5,860
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The Na
V
1.4 sodium channel is highly expressed in skeletal muscle, where it carries almost all of the inward Na
+
current that generates the action potential, but is not present at significant levels in other tissues. Consequently, mutations of SCN4A encoding Na
V
1.4 produce pure skeletal muscle phenotypes that now include six allelic disorders: sodium channel myotonia,
paramyotonia
congenita, hyperkalemic periodic paralysis, hypokalemic periodic paralysis, congenital myasthenia, and congenital myopathy with
hypotonia
. Mutation-specific alternations of Na
V
1.4 function explain the mechanistic basis for the diverse phenotypes and identify opportunities for strategic intervention to modify the burden of disease.
...
PMID:Sodium Channelopathies of Skeletal Muscle. 2893 73
The phenotypic spectrum associated with the skeletal muscle voltage-gated sodium channel gene (
SCN4A
) has expanded with advancements in genetic testing. Autosomal dominant
SCN4A
mutations were first linked to hyperkalemic periodic paralysis, then subsequently included
paramyotonia
congenita, several variants of myotonia, and finally hypokalemic periodic paralysis. Biallelic recessive mutations were later identified in myasthenic myopathy and in infants showing a severe congenital myopathy with
hypotonia
. We report a patient with a pathogenic
de novo SCN4A
variant, c.2386C>G p.L769V at a highly conserved leucine. The phenotype was manifest at birth with arthrogryposis multiplex congenita, severe episodes of bronchospasm that responded immediately to carbamazepine therapy, and electromyographic evidence of widespread myotonia. Another
de novo
case of p.L769V has been reported with hip dysplasia, scoliosis, myopathy, and later
paramyotonia
. Expression studies of L796V mutant channels showed predominantly gain-of-function changes, that included defects of slow inactivation. Computer simulations of muscle excitability reveal a strong predisposition to myotonia with exceptionally prolonged bursts of discharges, when the L796V defects are included. We propose L769V is a pathogenic variant, that along with other cases in the literature, defines a new dominant
SCN4A
disorder of myotonic myopathy with secondary congenital joint and skeletal involvement.
...
PMID:Myotonic Myopathy With Secondary Joint and Skeletal Anomalies From the c.2386C>G, p.L769V Mutation in
SCN4A
. 3226 24
