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

@article{Rojas1991AMM,
  title={A Met-to-Val mutation in the skeletal muscle Na+ channel $\alpha$-subunit in hyperkalaemic periodic paralysis},
  author={Cecilia V. Rojas and Jian-zhou Wang and L S Schwartz and Eric P. Hoffman and Berkley R. Powell and Robert Harold Brown},
  journal={Nature},
  year={1991},
  volume={354},
  pages={387-389}
}
HYPERKALAEMIC periodic paralysis (HYPP)1 is an autosomal dominant disease that results in episodic electrical inexcitability and paralysis of skeletal muscle. Electrophysiological data indicate that tetrodotoxin-sensitive sodium channels from muscle cells of HYPP-affected individuals show abnormal inactivation2,3. Genetic analysis of nine HYPP families has shown tight linkage between the adult skeletal muscle sodium channel α-subunit gene on chromosome 17q and the disease (lod score, z = 24… Expand
A novel sodium channel mutation in a family with hypokalemic periodic paralysis
TLDR
The identification of a mutation within the skeletal muscle sodium channel resulting in hypokalemic periodic paralysis represents a novel finding. Expand
Mutations in an S4 segment of the adult skeletal muscle sodium channel cause paramyotonia congenita
TLDR
The use of the single-strand conformation polymorphism technique is reported to be used to define alleles specific to PC patients from three families, establishing the chromosome 17q NaCh locus as the PC gene and representing two mutations causing the distinctive, temperature-sensitive PC phenotype. Expand
A double mutation in families with periodic paralysis defines new aspects of sodium channel slow inactivation.
TLDR
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. Expand
A novel mutation in the gene for the adult skeletal muscle sodium channel alpha-subunit (SCN4A) that causes paramyotonia congenita of von Eulenburg.
TLDR
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. Expand
Mutation in the S4 segment of the adult skeletal sodium channel gene in an Italian Paramyotonia Congenita (PC) family
TLDR
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. Expand
The α-subunit of the skeletal muscle sodium channel is encoded proximal to Tk-1 on mouse Chromosome 11
TLDR
Data from an interspecies backcross are consistent with the view that the conserved segment region may extend to the telomere on mouse Chr 11 and on human 17q, and incorporate an additional locus into the already considerable degree of homology observed for these human and mouse chromosomes. Expand
Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.
TLDR
The results prove that SCN4A, the gene encoding the sodium channel alpha subunit of skeletal muscle is responsible for HypoPP-2, a disease caused by enhanced channel inactivation and current reduction showing no myotonia. Expand
Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A.
TLDR
A complete penetrance in men and women, an early age at onset, postcritic myalgias and an increased number and severity of attacks induced by acetazolamide are observed in a large hypoPP family carrying an SCN4A mutation. Expand
Functional consequences of a Na+ channel mutation causing hyperkalemic periodic paralysis
TLDR
Patch-clamp recordings show that the human mutation introduced into the corresponding region of the rat muscle Na+ channel cDNA shifts the voltage dependence of activation by 10-15 mV in the negative direction, which results in a persistent Na+ current that activates near -70 mV; this phenomenon could underlie the abnormal muscle activity observed in patients with HYPP. Expand
Activation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation
TLDR
Results, showing that the I1495F and T704M hyperkalaemic periodic paralysis mutations both have profound effects on channel activation and fast–slow inactivation, suggest that the S5 segment maybe in a location where fast and slow inactivation converge. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 22 REFERENCES
Hyperkalemic periodic paralysis and the adult muscle sodium channel alpha-subunit gene.
TLDR
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. Expand
Confirmation of linkage of hyperkalaemic periodic paralysis to chromosome 17.
TLDR
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. Expand
Analysis in a large hyperkalemic periodic paralysis pedigree supports tight linkage to a sodium channel locus.
TLDR
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. Expand
A sodium channel defect in hyperkalemic periodic paralysis: Potassium-induced failure of inactivation
TLDR
The dominant expression of HPP is manifest by inactivation of the wild-type Na+ channel through the influence of the mutant gene product on membrane voltage, thereby inactivating normal Na+ channels, which are then unable to generate an action potential. Expand
Primary structure and functional expression of a mammalian skeletal muscle sodium channel
TLDR
The isolation and characterization of a cDNA encoding the alpha subunit of a new voltage-sensitive sodium channel, microI, from rat skeletal muscle is described, and northern blot analysis indicates that the 8.5 kb microI transcript is preferentially expressed in skeletal muscle. Expand
Primary structure and expression of a sodium channel characteristic of denervated and immature rat skeletal muscle
TLDR
It is suggested that SkM2 is a TTX-insensitive sodium channel expressed in both skeletal and cardiac muscle, similar to other recently cloned sodium channels from rat skeletal muscle. Expand
Molecular analysis of the para locus, a sodium channel gene in Drosophila
TLDR
The results support the conclusion that para encodes a functionally predominant class of sodium channels in Drosophila neurons and the para transcript appears to undergo alternative splicing to produce several distinct subtypes of this channel. Expand
Existence of distinct sodium channel messenger RNAs in rat brain
The sodium channel is a voltage-gated ionic channel essential for the generation of action potentials1–3. It has been reported that the sodium channels purified from the electric organ ofExpand
Genomic organization and deduced amino acid sequence of a putative sodium channel gene in Drosophila.
The deduced amino acid sequence of a Drosophila gene isolated with a vertebrate sodium channel complementary DNA probe revealed an organization virtually identical to the vertebrate sodium channelExpand
Changes in sodium channel gating produced by point mutations in a cytoplasmic linker.
TLDR
Group of two or three contiguous lysines were neutralized or a glutamate was substituted for an arginine in the III-IV linker of type III rat brain sodium channels, and inactivation occurred more rapidly rather than more slowly, contrary to predictions. Expand
...
1
2
3
...