title: Dinucleotide repeat polymorphisms at the SCN4A locus suggest allelic heterogeneity of hyperkalemic periodic paralysis and paramyotonia congenita.
abstract: Two polymorphic dinucleotide repeats--one (dGdA)n and one (dGdT)n--have been identified at the SCN4A locus, encoding the alpha-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.
authors.affiliation: Molecular Neurogenetics Laboratory, Massachusetts General Hospital, Charlestown 02129.
authors.forename: A I
authors.initials: AI
authors.lastname: McClatchey
authors.forename: J
authors.initials: J
authors.lastname: Trofatter
authors.forename: D
authors.initials: D
authors.lastname: McKenna-Yasek
authors.forename: W
authors.initials: W
authors.lastname: Raskind
authors.forename: T
authors.initials: T
authors.lastname: Bird
authors.forename: M
authors.initials: M
authors.lastname: Pericak-Vance
authors.forename: J
authors.initials: J
authors.lastname: Gilchrist
authors.forename: K
authors.initials: K
authors.lastname: Arahata
authors.forename: D
authors.initials: D
authors.lastname: Radosavljevic
authors.forename: H G
authors.initials: HG
authors.lastname: Worthen
mesh_terms: D000483:Alleles; D001483:Base Sequence; D008040:Genetic Linkage / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D006947:Hyperkalemia / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009224:Myotonia Congenita / Q000235:genetics*; D010245:Paralyses, Familial Periodic / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D015222:Sodium Channels