Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium-channel gene locus.
Paramyotonia congenita (PC), an autosomal dominant muscle disease, shares some clinical and electrophysiological similarities with another myotonic muscle disorder, hyperkalemic periodic paralysis (HYPP). However, clinical and electrophysiologic differences allow differentiation of the two disorders. The HYPP locus was recently shown to be linked to a skeletal muscle sodium-channel gene probe. We now report that PC maps to the same locus (LOD score 4.4, theta = 0 at assumed penetrance of .95). These linkage results, coupled with physiological data demonstrating abnormal sodium-channel function in patients with PC, implicate a sodium-channel gene as an important candidate for the site of mutation responsible for PC. Furthermore, this is strong evidence for the hypothesis that PC and HYPP are allelic disorders.
Ptacek
L J
LJ
Department of Neurology, University of Utah School of Medicine, Salt Lake City 84132.
Trimmer
J S
JS
Agnew
W S
WS
Roberts
J W
JW
Petajan
J H
JH
Leppert
M
M
D015342:DNA Probes / Q000235:genetics; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D006947:Hyperkalemia / Q000235:genetics / Q000503:physiopathology; D008126:Lod Score; D008297:Male; D009132:Muscles / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009224:Myotonia Congenita / Q000235:genetics* / Q000503:physiopathology; D010245:Paralyses, Familial Periodic / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D015222:Sodium Channels / Q000235:genetics*
D015342:DNA Probes; D015222:Sodium Channels