A novel sodium channel mutation causing a hyperkalemic paralytic and paramyotonic syndrome with variable clinical expressivity

@article{Wagner1997ANS,
  title={A novel sodium channel mutation causing a hyperkalemic paralytic and paramyotonic syndrome with variable clinical expressivity},
  author={S Wagner and Holger Lerche and Nenad Mitrovi{\'c} and R. Heine and A. L. George and Frank Lehmann-Horn},
  journal={Neurology},
  year={1997},
  volume={49},
  pages={1018 - 1025}
}
A point mutation A4078G predicting the amino acid exchange Met1360Val in segment IV/S1 of the human muscle sodium channel α-subunit was identified in a family presenting features of hyperkalemic periodic paralysis and paramyotonia congenita with sex-related modification of expression. In this family, only one male member is clinically affected, presenting episodes of flaccid weakness as well as paradoxical myotonia and cold-induced weakness. Three female family members who have the same… 

Figures from this paper

Mechanisms of cold sensitivity of paramyotonia congenita mutation R1448H and overlap syndrome mutation M1360V

Missense mutations of the human skeletal muscle voltage‐gated Na+ channel (hSkM1) cause a variety of neuromuscular disorders. The mutation R1448H results in paramyotonia congenita and causes

Hyperkalemic periodic paralysis and paramyotonia congenita – A novel sodium channel mutation –

A case of HyperPP and PC with novel point mutation on the SCN4A gene, which could be pathogenic, is reported and myotonia of the face and fingers induced by cold water or inside a cold room (4 °C) could be increased with repeated contraction.

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.

Lack of sodium channel mutation in an Italian family with paramyotonia congenita.

The existence of a second gene different from SCN4A that can give rise to a clinical PC phenotype can be speculated upon.

Hyperkalemic periodic paralysis M1592V mutation modifies activation in human skeletal muscle Na+ channel.

The functional properties of the M1592V mutant resemble those of the previously characterized HPP T704M mutant, both clinically similar phenotypes arise from mutations located at a distance from the putative voltage sensor of the channel.

Hyperkalemic periodic paralysis M1592V mutation modifies activation in human skeletal muscle Na+ channel.

The functional properties of the M1592V mutant resemble those of the previously characterized HPP T704M mutant, both clinically similar phenotypes arise from mutations located at a distance from the putative voltage sensor of the channel.

N1366S mutation of human skeletal muscle sodium channel causes paramyotonia congenita

It is demonstrated that N1366S is a disease‐causing mutation and that the temperature‐sensitive alteration of N1365S channel activity may be responsible for the pronounced paramyotonia congenita symptoms of these patients.

Mutant channels contribute <50% to Na+ current in paramyotonia congenita muscle.

Comparing the gating defects of two human muscle Na+ channel mutants causing paramyotonia congenita in native muscle specimens from two patients with those of the same mutant recombinant channels expressed in human embryonic kidney cells raises the possibility that variability in the ratio of mutant to wild-type Na+ channels in the muscle membrane has an impact on the clinical severity of the phenotype.

Hypokalaemic periodic paralysis and myotonia in a patient with homozygous mutation p.R1451L in NaV1.4

The data suggest that recessive loss-of-function NaV1.4 variants can present with hypoPP without congenital myopathy or myasthenia and that myotonia can present even in carriers of homozygous NaV 1.4 loss- of-function mutations.
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