Linkage data suggesting allelic heterogeneity for paramyotonia congenita and hyperkalemic periodic paralysis on chromosome 17

Hum Genet. 1991 Nov;88(1):71-4. doi: 10.1007/BF00204932.

Abstract

Paramyotonia congenita (PC), an autosomal dominant non-progressive muscle disorder, is characterised by cold-induced stiffness followed by muscle weakness. The weakness is caused by a dysfunction of the sodium channel in muscle fibre. Parts of the gene coding for the alpha-subunit of the sodium channel of the adult human skeletal muscle (SCN4A) have been localised on chromosome 17. To investigate the role of this gene in the etiology of PC, a linkage analysis in 17 well-defined families was carried out. The results (zeta = 20.61, theta = 0.001) show that the mutant gene responsible for the disorder is indeed tightly linked to the SCN4A gene. The mutation causing hyperkalemic periodic paralysis (HyperPP) with myotonia has previously been mapped to this gene locus by the same candidate gene approach. Thus, our data suggest that PC and HyperPP are caused by allelic mutations at a single locus on chromosome 17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Chromosomes, Human, Pair 17*
  • Female
  • Genetic Linkage*
  • Humans
  • Hyperkalemia / genetics*
  • Lod Score
  • Male
  • Mutation
  • Myotonia Congenita / genetics*
  • Paralyses, Familial Periodic / genetics*
  • Pedigree
  • Sodium Channels / genetics*

Substances

  • Sodium Channels