Temperature-sensitive mutations in the III–IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita

@article{McClatchey1992TemperaturesensitiveMI,
  title={Temperature-sensitive mutations in the III–IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita},
  author={Andrea I. McClatchey and Peter van den Bergh and Margaret A. Pericak-Vance and Wendy H. Raskind and Christine Verellen and Diane M. McKenna-Yasek and Keshav Rao and Jonathan L. Haines and T Bird and Robert H. Brown and James F. Gusella},
  journal={Cell},
  year={1992},
  volume={68},
  pages={769-774}
}

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).

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.

Functional characterization and cold sensitivity of T1313A, a new mutation of the skeletal muscle sodium channel causing paramyotonia congenita in humans

The results confirm the role of T1313 residue in Na+ channel fast inactivation, and unveil subtle changes in other gating processes that may influence the clinical phenotype.

Human sodium channel myotonia: slowed channel inactivation due to substitutions for a glycine within the III‐IV linker.

Electrophysiological and molecular genetic studies strongly suggest that three dominant point mutations discovered at the same nucleotide position of the SCN4A gene encoding the adult skeletal muscle Na+ channel alpha‐subunit cause myotonia.

A1152D mutation of the Na+ channel causes paramyotonia congenita and emphasizes the role of DIII/S4–S5 linker in fast inactivation

A new PC‐associated mutation is identified, which substitutes aspartic acid for a conserved alanine in the S4–S5 linker of domain III of the human skeletal muscle Na+ channel (A1152D).

A novel mutation in the gene for the adult skeletal muscle sodium channel alpha-subunit (SCN4A) that causes paramyotonia congenita of von Eulenburg.

4 mutations that cause a decrease in positive charge in the S4/D4 are associated with the phenotype of PMC of von Eulenburg, providing an important genotype-phenotype correlation in sodium channelopathies.
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References

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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.

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.

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.

Dinucleotide repeat polymorphisms at the SCN4A locus suggest allelic heterogeneity of hyperkalemic periodic paralysis and paramyotonia congenita.

The identification of polymorphic dinucleotide repeats at the SCN4A locus, encoding the alpha-subunit of the adult skeletal muscle sodium channel, confirms the genetic linkage of hyperkalemic periodic paralysis and paramyotonia congenita, distinct neuromuscular disorders, and indicates the strong likelihood of allelic heterogeneity in both disorders.

Altered sodium channel behaviour causes myotonia in dominantly inherited myotonia congenita