Biomaterial Database

Linkage of malignant hyperthermia and hyperkalemic periodic paralysis to the adult skeletal muscle sodium channel (SCN4A) gene in a large pedigree. 1998

R Moslehi, and S Langlois, and I Yam, and J M Friedman

Department of Medical Genetics, University of British Columbia and British Columbia Children's Hospital, Vancouver, Canada.

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.

UI	MeSH Term	Description	Entries
D008040	Genetic Linkage	The co-inheritance of two or more non-allelic GENES due to their being located more or less closely on the same CHROMOSOME.	Genetic Linkage Analysis,Linkage, Genetic,Analyses, Genetic Linkage,Analysis, Genetic Linkage,Genetic Linkage Analyses,Linkage Analyses, Genetic,Linkage Analysis, Genetic
D008126	Lod Score	The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds."	Lod Scores,Score, Lod,Scores, Lod
D008297	Male		Males
D008305	Malignant Hyperthermia	Rapid and excessive rise of temperature accompanied by muscular rigidity following general anesthesia.	Hyperpyrexia, Malignant,Hyperthermia, Malignant,Malignant Hyperpyrexia,Anesthesia Related Hyperthermia,Hyperthermia of Anesthesia,Anesthesia Hyperthermia,Hyperthermia, Anesthesia Related,Malignant Hyperpyrexias
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D010245	Paralyses, Familial Periodic	A heterogenous group of inherited disorders characterized by recurring attacks of rapidly progressive flaccid paralysis or myotonia. These conditions have in common a mutation of the gene encoding the alpha subunit of the sodium channel in skeletal muscle. They are frequently associated with fluctuations in serum potassium levels. Periodic paralysis may also occur as a non-familial process secondary to THYROTOXICOSIS and other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1481)	Normokalemic Periodic Paralysis,Periodic Paralysis, Familial,Familial Periodic Paralysis,Familial Periodic Paralyses,Normokalemic Periodic Paralyses,Paralyses, Normokalemic Periodic,Paralysis, Familial Periodic,Paralysis, Normokalemic Periodic,Periodic Paralyses, Familial,Periodic Paralyses, Normokalemic,Periodic Paralysis, Normokalemic
D010375	Pedigree	The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.	Family Tree,Genealogical Tree,Genealogic Tree,Genetic Identity,Identity, Genetic,Family Trees,Genealogic Trees,Genealogical Trees,Genetic Identities,Identities, Genetic,Tree, Family,Tree, Genealogic,Tree, Genealogical,Trees, Family,Trees, Genealogic,Trees, Genealogical
D012150	Polymorphism, Restriction Fragment Length	Variation occurring within a species in the presence or length of DNA fragment generated by a specific endonuclease at a specific site in the genome. Such variations are generated by mutations that create or abolish recognition sites for these enzymes or change the length of the fragment.	RFLP,Restriction Fragment Length Polymorphism,RFLPs,Restriction Fragment Length Polymorphisms
D002886	Chromosomes, Human, Pair 17	A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.	Chromosome 17
D002888	Chromosomes, Human, Pair 19	A specific pair of GROUP F CHROMOSOMES of the human chromosome classification.	Chromosome 19