Abstract
Two polymorphic dinucleotide repeats–one (dGdA)
n
and one (dGdT)
n
–have been identified at the
SCN4A
locus, encoding the α-subunit of the adult skeletal muscle sodium channel. When typed using PCR, the dinucleotide repeats display 4 and 10 alleles, respectively, with a predicted heterozygosity of .81 for the combined haplotype. We have applied these polymorphisms to the investigation of hyperkalemic periodic paralysis and paramyotonia congenita, distinct neuromuscular disorders both of which are thought to involve mutation at
SCN4A
. Our data confirm the genetic linkage of both disorders with
SCN4A
. Haplotype analysis also indicates the strong likelihood of allelic heterogeneity in both disorders.
