论文信息 - Hypokalemic Periodic Paralysis andtheDihydropyridine Receptor (CACNLIA3):Genotype/Phenotype Correlations forTwo Predominant Mutations andEvidence fortheAbsenceofa Founder Effect in16Caucasian Families

Hypokalemic Periodic Paralysis andtheDihydropyridine Receptor (CACNLIA3):Genotype/Phenotype Correlations forTwo Predominant Mutations andEvidence fortheAbsenceofa Founder Effect in16Caucasian Families

Summary Hypokalemic periodic paralysis (hypoPP) isanautosomal dominant disorder belonging toagroup ofmuscle diseases involving theabnormal function ofionchannels. This group ofmuscle diseases also comprises hyperkalemic periodic paralysis andparamyotonia congenita, bothsodiumchannel diseases, andmyotonia congenita, achloridechannel disorder. HypoPP ischaracterized byacute attacks ofmuscle weakness concomitant with afall inblood potassiumlevels. Werecently localized thehypoPP locus (hypoPP1) tochromosome 1q31-32, inaninterval where the alsubunit ofthedihydropyridine receptor calcium channel(CACNL1A3) also maps. Subsequently, deleterious mutations inthevoltage-sensor segment S4werefound, establishing thedihydropyridine receptor CACNL1A3as thecausative geneforhypoPP. Inthis paper, wereport thestudy of16hypoPP families ofCaucasian origin. We foundonlytwo mutations-Arg528His and Arg1239His-that cosegregated with hypoPP, each inhalf ofthefamilies. Analysis oftheclinical characteristics of both groups offamilies demonstrated that incomplete penetrance isadistinctive feature oftheArg528His mutation. Using dinucleotide repeats contained within orclose tothe dihydropyridine receptor gene, inconjunction withevidence ofadenovoArg1239His mutation, weshowthat afounder effect isunlikely toaccount forthetwopredominant mutations.

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