Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita

@article{Ptek1992MutationsIA,
  title={Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita},
  author={Louis J. Pt{\'a}{\vc}ek and Alfred L. George and Robert L. Barchi and Robert C. Griggs and Jack E. Riggs and Margaret Robertson and M. Leppert},
  journal={Neuron},
  year={1992},
  volume={8},
  pages={891-897}
}
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243 Citations
Highly Influential Citations
10
Background Citations
58
Methods Citations
4

243 Citations

Mutation in the S4 segment of the adult skeletal sodium channel gene in an Italian Paramyotonia Congenita (PC) family

A mutation in an S4 segment of the adult skeletal muscle sodium channel in a clinically-defined Italian family is described that leads to the paramyotonia congenita (PC) phenotype with dominant autosomal inheritance and temperature-related symptoms (regional weakness following cooling and exercise), present since childhood in all of the affected family members.

Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis

Five other HYPP and PC families have been ascertained, and previously reported sodium channel mutations have been identified in each, and an additional mutation is reported, a leucine ‐ arginine substirution in the ss segment of domain 4 (L1433R), that results in the PC phenotype.

Novel mutations in families with unusual and variable disorders of the skeletal muscle sodium channel

Two mutations in SCN4A which affect regions of the sodium channel not previously associated with a disease phenotype are found, causing affected family members to display an unusual mixture of clinical features reminiscent of PMC, HPP and of a third disorder, myotonia congenita (MC).

A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation.

One allele with two novel mutations occurring simultaneously in the SCN4A gene, encoding the human skeletal muscle voltage-gated Na(+) channel, is identified, demonstrating that manifestation of HyperKPP does not necessarily require disruption of slow inactivation.

A novel muscle sodium channel mutation causes painful congenital myotonia

A novel SCN4A mutation causing the replacement of Val445 in the sixth transmembrane segment of domain 1 with methionine was discovered in all affected individuals and is the likely genetic basis for the syndrome.

Hyperkalemic periodic paralysis

A novel procedure is described, using ligase chain reaction (LCR), to simultaneously identify two different point mutations and one rare, apparently benign polymorphism that results in a nonconservative amino acid substitution in hyperkalemic periodic paralysis.

Paramyotonia congenita: genotype to phenotype correlations in two families and report of a new mutation in the sodium channel gene

Characterization of a new sodium channel mutation at arginine 1448 associated with moderate paramyotonia congenita in humans

The data show that the defects observed in the sodium channel function could well explain the onset of the paramyotonia congenita in this family and emphasize the role of segment S4 of domain IV in sodium channel inactivation.

Muscle sodium channel inactivation defect in paramyotonia congenita with the thr1313met mutation

Molecular basis of Thomsen's disease (autosomal dominant myotonia congenita)

Findings establish HUMCLC as the Thomsen's disease gene, which results in the substitution of a glutamic acid for a glycine residue located between the third and fourth predicted membrane spanning segments.
...

References

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Identification of a mutation in the gene causing hyperkalemic periodic paralysis

A Met-to-Val mutation in the skeletal muscle Na+ channel α-subunit in hyperkalaemic periodic paralysis

An A - G substitution in the patient's messenger RNA that causes a Met-Val change in a highly conserved region of the α-subunit, predicted to be in a transmembrane domain is identified and discovered a voltage-gated channel mutation responsible for a human genetic disease.

Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium-channel gene locus.

Linkage results implicate a sodium-channel gene as an important candidate for the site of mutation responsible for PC, and provide strong evidence for the hypothesis that PC and HYPP are allelic disorders.

Paramyotonia congenita and hyperkalemic periodic paralysis are linked to the adult muscle sodium channel gene

The hypothesis that hyperkalemic periodic paralysis (without myotonia) and paramyotonia congenita are tightly linked to the tetrodotoxin‐sensitive adult skeletal muscle sodium channel gene on chromosome 17q23‐25 in two large pedigrees is tested.

Confirmation of linkage of hyperkalaemic periodic paralysis to chromosome 17.

Linkage studies were performed in six European families with hyperkalaemic periodic paralysis with myotonia, suggesting that the disease is caused by dominant mutations of the adult sodium channel, and that it is probably a genetically homogeneous disorder.

Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene.

Parts of the adult muscle sodium channel alpha-subunit gene were cloned and mapped near the human growth hormone locus (GH1) on chromosome 17 and showed tight linkage to the genetic defect with no recombinants detected.

Analysis in a large hyperkalemic periodic paralysis pedigree supports tight linkage to a sodium channel locus.

Close genetic linkage between an NaCh gene and the HYPP locus in another family is demonstrated and the absence of any obligate recombinations in the two families strengthens the argument that this Na Ch gene is the site of the defect in this disorder.

Linkage of atypical myotonia congenita to a sodium channel locus

The molecular alteration causing acetazolamide-responsive myotonia congenita is likely an allelic defect in this human, skeletal-muscle, sodium channel gene.

Primary structure of the adult human skeletal muscle voltage‐dependent sodium channel

The cloning and nucleotide sequence determination of the normal product of the SCN4A gene product is reported, which is the human homologue of rSkM1, the tetrodotoxin‐sensitive sodium channel characteristic of adult rat skeletal muscle.

Multiple mutations in highly conserved residues are found in mildly affected cystic fibrosis patients