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 Jianzhou Wang and L S Schwartz and Eric P. Hoffman and Berkley R. Powell and Robert H. 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… 

A novel sodium channel mutation in a family with hypokalemic periodic paralysis

The identification of a mutation within the skeletal muscle sodium channel resulting in hypokalemic periodic paralysis represents a novel finding.

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 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.

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.

The α-subunit of the skeletal muscle sodium channel is encoded proximal to Tk-1 on mouse Chromosome 11

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.

Voltage-sensor sodium channel mutations cause hypokalemic periodic paralysis type 2 by enhanced inactivation and reduced current.

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.

Hypokalaemic periodic paralysis type 2 caused by mutations at codon 672 in the muscle sodium channel gene SCN4A.

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.

Activation and Inactivation of the Voltage-Gated Sodium Channel: Role of Segment S5 Revealed by a Novel Hyperkalaemic Periodic Paralysis Mutation

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.
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