Identification of a mutation in the gene causing hyperkalemic periodic paralysis

@article{Ptek1991IdentificationOA,
  title={Identification of a mutation in the gene causing hyperkalemic periodic paralysis},
  author={Louis J. Pt{\'a}{\vc}ek and Alfred L. George and Robert Griggs and Rabi Tawil and Roland G. Kallen and Robert L. Barchi and Margaret Robertson and M. Leppert},
  journal={Cell},
  year={1991},
  volume={67},
  pages={1021-1027}
}
DNA from seven unrelated patients with hyperkalemic periodic paralysis (HYPP) was examined for mutations in the adult skeletal muscle sodium channel gene (SCN4A) known to be genetically linked to the disorder. Single-strand conformation polymorphism analysis revealed aberrant bands that were unique to three of these seven patients. All three had prominent fixed muscle weakness, while the remaining four did not. Sequencing the aberrant bands demonstrated the same C to T transition in all three… Expand
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References

SHOWING 1-10 OF 41 REFERENCES
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
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
Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium-channel gene locus.
TLDR
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. Expand
Multiple mutations in highly conserved residues are found in mildly affected cystic fibrosis patients
TLDR
Three different point mutations in the coding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene are identified and provide important clues to functionally important regions of the molecule. Expand
Identification and characterization of the familial adenomatous polyposis coli gene
TLDR
DNA from 61 unrelated patients with adenomatous polyposis coli (APC) was examined for mutations in three genes located within a 100 kb region deleted in two of the patients, and data have established that DP2.5 is the APC gene. Expand
Linkage of atypical myotonia congenita to a sodium channel locus
TLDR
The molecular alteration causing acetazolamide-responsive myotonia congenita is likely an allelic defect in this human, skeletal-muscle, sodium channel gene. Expand
A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations
TLDR
The TBR gene is established as the NF1 gene and a description of a major segment of the gene is provided, indicating base pair changes in the gene. Expand
Progressive myopathy in hyperkalemic periodic paralysis.
TLDR
The authors' experience suggests that a progressive myopathy is as common in hyperkalemic periodic paralysis as it is in the hypokalemic 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
Altered sodium channel behaviour causes myotonia in dominantly inherited myotonia congenita
TLDR
It is concluded that in myotonia congenita re-openings of Na+ channels are the major cause of hyperexcitability and that Cl- conductance is normal and if it is reduced in rare cases, it may potentiate the myOTonia. Expand
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