Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.

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Citation

McClatchey AI, Van den Bergh P, Pericak-Vance MA, Raskind W, Verellen C, McKenna-Yasek D, Rao K, Haines JL, Bird T, Brown RH Jr, et al.

Temperature-sensitive mutations in the III-IV cytoplasmic loop region of the skeletal muscle sodium channel gene in paramyotonia congenita.

Cell. 1992 Feb 21;68(4):769-74.

PubMed ID
1310898 [ View in PubMed
]
Abstract

Paramyotonia congenita (PMC), a dominant disorder featuring cold-induced myotonia (muscle stiffness), has recently been genetically linked to a candidate gene, the skeletal muscle sodium channel gene SCN4A. We have now established that SCN4A is the disease gene in PMC by identifying two different single-base coding sequence alterations in PMC families. Both mutations affect highly conserved residues in the III-IV cytoplasmic loop, a portion of the sodium channel thought to pivot in response to membrane depolarization, thereby blocking and inactivating the channel. Abnormal function of this cytoplasmic loop therefore appears to produce the Na+ current abnormality and the unique temperature-sensitive clinical phenotype in this disorder.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Sodium channel protein type 4 subunit alphaP35499Details