Hypokalemic Periodic Paralysis andtheDihydropyridine Receptor (CACNLIA3):Genotype/Phenotype Correlations forTwo Predominant Mutations andEvidence fortheAbsenceofa Founder Effect in16Caucasian Families
msra(1995)
摘要
Summary Hypokalemic periodic paralysis (hypoPP) isanautosomal dominant disorder belonging toagroup ofmuscle diseases involving theabnormal function ofionchannels. This group ofmuscle diseases also comprises hyperkalemic peri- odic paralysis andparamyotonia congenita, bothsodium- channel diseases, andmyotonia congenita, achloride- channel disorder. HypoPP ischaracterized byacute attacks ofmuscle weakness concomitant with afall inblood potas- siumlevels. Werecently localized thehypoPP locus (hy- poPP1) tochromosome 1q31-32, inaninterval where the alsubunit ofthedihydropyridine receptor calcium chan- nel(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 pen- etrance isadistinctive feature oftheArg528His mutation. Using dinucleotide repeats contained within orclose tothe dihydropyridine receptor gene, inconjunction withevi- dence ofadenovoArg1239His mutation, weshowthat afounder effect isunlikely toaccount forthetwopredomi- nant mutations.
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founder effect
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