Different gene loci for hyperkalemic and hypokalemic periodic paralysis.
The periodic paralyses are dominantly inherited disorders in which patients acutely develop muscle weakness in association with changes in the level of blood potassium. We recently reported genetic linkage of hyperkalemic periodic paralysis (HIKPP) to the gene encoding the adult form of the skeletal muscle sodium channel on the long arm of chromosome 17. In this paper, we exclude genetic linkage between hypokalemic periodic paralysis (HOKPP) and this sodium channel gene, demonstrating that there is non-allelic genetic heterogeneity among different forms of periodic paralysis. Electrophysiological abnormalities in muscle sodium conductance have been reported for both HIKPP and HOKPP as well as other muscle disorders characterized by membrane hyperexcitability or myotonia (myotonia congenita, paramyotonia congenita and the Schwartz-Jampel syndrome). The possibility that there may be a family of human muscle diseases arising from mutations in the sodium channel suggests these disorders may be classified by categories of mutations within this critical voltage-sensitive membrane protein.
Fontaine
B
B
Molecular Neurogenetics Laboratory, Massachusetts General Hospital, Charlestown.
Trofatter
J
J
Rouleau
G A
GA
Khurana
T S
TS
Haines
J
J
Brown
R
R
Gusella
J F
JF
D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D006947:Hyperkalemia / Q000150:complications / Q000235:genetics*; D007008:Hypokalemia / Q000150:complications / Q000235:genetics*; D008126:Lod Score; D008297:Male; D010245:Paralyses, Familial Periodic / Q000097:blood / Q000235:genetics*; D010375:Pedigree