Genotype-phenotype correlations in human skeletal muscle sodium channel diseases
R. Rudel, K. Ricker and F. Lehmann-Horn
Department of Physiology, University of Ulm, Germany.
BACKGROUND: Over the past 3 years, the genetics of the myotonic diseases
have been substantially elaborated. Three genetically different groups of
myotonic disease can be discerned: (1) the chloride channel myotonias, (2)
the adynamia-paramyotonia complex, and (3) myotonic dystrophy. METHODS AND
RESULTS: Electrophysiology has suggested and molecular biology has proven
that the diseases belonging to the adynamia-paramyotonia complex, ie,
paramyotonia congenita, hyperkalemic and normokalemic periodic paralysis,
and some rare forms of myotonic disease, are caused by point mutations in
the gene encoding the alpha subunit of the sodium channel in adult human
skeletal muscle, located on chromosome 17q23. Thirteen different mutations
have been described by various groups in the United States and Germany. The
various mutations causing a particular form of the complex are not located
in the gene in a predictable or easily understandable regular manner.
CONCLUSIONS: Further study of the genotype-phenotype correlations should
not only increase our understanding of the variability of signs in this
group of diseases, it could also provide us with a deeper insight in the
function of the various regions of the sodium channel protein.
