HYPERKALEMIC PERIODIC PARALYSIS - RAPID MOLECULAR DIAGNOSIS AND RELATIONSHIP OF GENOTYPE TO PHENOTYPE IN 12 FAMILIES

We studied mutations of the adult voltage-gated skeletal muscle sodium channel gene in 12 families, from diverse ethnic backgrounds, with hy perkalemic periodic paralysis (HyperPP). We describe a novel procedure , using ligase chain reaction (LCR), to simultaneously identify two di fferent point mutations (previously described) and one rare, apparentl y benign polymorphism that results in a nonconservative amino acid sub stitution. Three of 12 families showed the Met1592Val mutation, and si x of 12 had the Thr704Met mutation. The mutation in three of the 12 fa milies was not identified. In one of these three families, the disease was not linked to the adult voltage-gated sodium channel gene, sugges ting the existence of a clinically similar but genetically distinct fo rm of HyperPP. Genotype/phenotype correlations based on patient record s and interviews in these families showed the variable and subjective nature of the illness, although the clinical distinctions between hype rkalemic periodic paralysis and paramyotonia congenita were reinforced by the molecular data.