Linkage of malignant hyperthermia and hyperkalemic periodic paralysis to the adult skeletal muscle sodium channel (SCN4A) gene in a large pedigree.
Hyperkalemic periodic paralysis (HPP) is caused by mutations of the adult skeletal muscle sodium channel (SCN4A) gene on chromosome 17. Malignant hyperthermia (MH) is a genetically heterogeneous autosomal-dominant disorder occurring in association with various neuromuscular diseases or without other apparent abnormalities. In some families, MH is associated with mutations of a calcium release channel (RYR1) gene on chromosome 19. In other families, linkage of this disorder to the SCN4A gene on chromosome 17 has been suggested. We report on linkage analysis in a family in which both HPP and MH are inherited as autosomal-dominant traits. Two polymorphisms within the SCN4A locus, an RFLP and a (C-A)n repeat, were typed on multiple family members. The findings were consistent with linkage of the polymorphic markers within the SCN4A gene to both HPP (Zmax = 6.79 at theta = 0.0) and MH (Zmax = 1.76 at theta = 0) in this family. Our data provide further evidence that MH is linked to the SCN4A locus in some families.
Moslehi
R
R
Department of Medical Genetics, University of British Columbia and British Columbia Children's Hospital, Vancouver, Canada.
Langlois
S
S
Yam
I
I
Friedman
J M
JM
D000328:Adult; D001483:Base Sequence; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D018900:Dinucleotide Repeats; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006801:Humans; D006947:Hyperkalemia / Q000150:complications / Q000235:genetics*; D008126:Lod Score; D008297:Male; D008305:Malignant Hyperthermia / Q000150:complications / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D062553:NAV1.4 Voltage-Gated Sodium Channel; D010245:Paralyses, Familial Periodic / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D015222:Sodium Channels / Q000235:genetics*
D017931:DNA Primers; D062553:NAV1.4 Voltage-Gated Sodium Channel; C106251:SCN4A protein, human; D015222:Sodium Channels