anti-Sodium Channel, Voltage-Gated, Type IV, alpha Subunit (SCN4A) Antibodies

Mouse (Murine) Sodium Channel, Voltage-Gated, Type IV, alpha Subunit (SCN4A) interaction partners

1. we performed an unbiased mutagenesis screen on an HD mouse model, identifying a mutation in the skeletal muscle voltage-gated sodium channel (Scn4a, termed 'draggen' mutation) as a novel disease enhancer

2. NaV1.4 null mice have latent myasthenia and a right shift of the force-stimulus relation, without evidence of periodic paralysis. Sodium current density was half that of wild-type muscle and no compensation by retained expression of the foetal NaV1.5 isoform was detected. Mice null for NaV1.4 did not survive beyond the second postnatal day.

3. In-depth characterization of draggen mice uncovered novel systemic metabolic abnormalities in Scn4a mouse models and provided novel insights into disease mechanisms

4. HyperKPP phenotype does not depend solely on the NaV1.4 content.

5. Homozygous R669H mice had a robust hypokalemic periodic paralysis phenotype, with transient loss of muscle excitability and weakness in low-K+ challenge, insensitivity to high-K+ challenge, dominant inheritance, and absence of myotonia.

6. A distinct autosomal recessive myotonic mouse in the C57BL/6 background (line B6MT)is reported in which the Scn4a gene shows polymorphism with no functional consequences.

7. The skeletal muscle isoform of Na(v)1.4, which represents over 90% of voltage-gated sodium channels in muscle, plays an important role in development of abnormally high Na(+) concentrations found in muscle from mdx mice.

Human Sodium Channel, Voltage-Gated, Type IV, alpha Subunit (SCN4A) interaction partners

1. A Ca(2+)-dependent CaM N-lobe binding site previously identified in NaV1.5 is not present in NaV1.4 allowing the N-lobe to signal other regions of the NaV1.4 channel.

2. To identify novel disease modifiers, we performed an unbiased mutagenesis screen on an HD mouse model, identifying a mutation in the skeletal muscle voltage-gated sodium channel (Scn4a, termed 'draggen' mutation) as a novel disease enhancer. Double mutant mice (HD; Scn4aDgn/+) had decreased survival, weight loss and muscle atrophy

3. this study reports the cryo-electron microscopy structure of the human Nav1.4-beta1 complex at 3.2-A resolution.

4. R1451 pathogenic mutations shifted the inactivation kinetics and reduced the current density.

5. structural basis for gating pore current in periodic paralysis; results reveal pathogenic mechanisms of periodic paralysis at the atomic level and suggest designs of drugs that may prevent ionic leak and provide symptomatic relief from hypokalaemic and normokalaemic periodic paralysis

6. Rare SCN4A variants that directly alter NaV1.4 function occur in infants who had died from SIDS. These variants are predicted to significantly alter muscle membrane excitability and compromise respiratory and laryngeal function.

7. We report on 3 brothers presenting a peculiar clinical and histopathologic phenotype characterized by facial weakness with ptosis and a mild dystrophic pattern associated with recessive SCN4A mutations.

8. Paramyotonia congenita-causing mutation N1366S leads to a gain-of-function change of NaV1.4 gating in response to cold.

9. Data suggest that mutation of the sodium channel, voltage-gated, type IV, alpha protein (SCN4A) gene probably underlies the hypokalemic periodic paralysis in the family.

10. We identified a novel Nav 1.4 mutation I692M in 14 families out of the 104 genetically identified Hyperkalemic periodic paralysis (HyperPP) families in the Neuromuscular Centre Ulm and is therefore as frequent as I693T (13 families out of 14 HyperPP families) in Germany. Surprisingly, in 13 families, a known polymorphism S906T was also present

11. Combining our results with the literature on Chinese populations indicates that 21 mutations in CLCN1 have been associated with myotonia congenital, while 7 mutations in SCN4A have been associated with paramyotonia congenita, 2 mutations in SCN4A have been associated with sodium channel myotonias.

12. A rare variant p.Pro1629Leu in SCN4A identified in a patient with a skeletal muscle deficit and intermittent dysphagia.

13. Cohort of 30 patients carrying the c.3466G>A p.A1156T mutation in the SCN4A gene showed a consistent phenotype of predominant myalgia, muscle stiffness, and exercise cramps without signs of clinical myotonia, paramyotonia, or periodic paralyses; modest gain in the function of p.A1156T channel in whole-cell patch clamp studies may explain the absence of clinical myotonia

14. These data suggest a possible involvement of SCN4A variants in the pathophysiological mechanism underlying the development of a spontaneous or drug-induced type 1 electrocardiographic pattern and the occurrence of malignant arrhythmias in some patients with Brugada syndrome.

15. association of the genetic variability of SCN4A with the development of essential tremor

16. Computer simulations of the effects of the I693T mutation were introduced in the muscle fiber model by both hyperpolarizing shifts in the Nav1.4 channel activation and a faster recovery from slow channel inactivation

17. CACNA1S and SCN4A mutations are relatively rare in patients with hypokalemic periodic paralysis

18. Recessive loss-of-function SCN4A mutations were identified in congenital myopathy patients.

19. The c.4427 T>C (p.Met1476Thr) mutation of the SCN4A gene contribute to the paramyotonia congenita.

20. Mutation analysis in the patient and in child's mother revealed a heterozygous p.N1180I mutation in exon 19 of SCN4A gene. In newborns with stiffness, peripheral contractures and myotonia, the sequence analysis of SCN4A gene should be performed.