| Background As one form of ion channelopathies, periodic paralyses (PP) are a group of autosomal dominant familial disorders involving the abnormal function of ion channels and they are characterized by paralysis attacks of varying severity, accompanied by a change in blood potassium levels. The diseases may have their onset at any time from infancy or childhood to the third decades of life. During attacks, muscles of the lower extremities are initially affected, followed by the lower trunk and arms, and even dyspnea or cardiac arrhythmia. The etiology and nosogenesis of the diseases are not clear enough to have a very effective therapeutic tool or preventive measure. The progresses in molecular biology on three types of periodic paralyses are as follows: (1) Hypokalemic periodic paralysis(hypoKPP) is mainly related to the mutation in the muscle dihydropyridine-sensitive calcium channel a l-subunit(CACNAlS), and less the muscle sordium channel a 1-subunit (SCN4A), but the mechanisms of hypokalemia are yet not clear, (2)hyperkalemic periodic paralysis (hyperKPP) is caused by the missense mutation of SCN4A gene, but the detailed mechanisms of the mutation influencing membrane potential are not very clear. (3)The genetic researches on normokalemic periodic paralysis (normoKPP) are very few, and the relationship between normoKPP and hyperKPP is still in doubts. (4) In China, the genetic researches on three types of periodic paralyses are still inabsence, and the mode of gene mutation with Chinese PP patients is not clear. In this research we aim to clarify the clinical and genetic features of three types of PP with Chinese patients. This research is devided into three parts. PART ONE: Collecting and characterizing the genetic resources for periodic paralyses, and establishing the process of scanning SCN4A gene and CACNA1S gene for disease-related mutationThe objective of this study was to establish a repository for blood DNA samples accompanied with clinical and pedigree data. In this study, we firstly established a network for collecting genetic resources of three types of PP in China. With this network, we collected 25 normoKPP patients in 11 unrelated families in which three were with family history, and eight were scattered cases, seven patients in one hyperKPP family, and 34 hypoKPP patients in which six were with family history, and 28 were scattered cases. All these invaluable resources were important for the genetic researches on periodic paralyses.Secondly, we designed primers for all 24 exons of SCN4A gene, and exon 11 and exon 30 of CACNA1S gene with the help of the website http://www.ncbi.nlm.nih.gov/ of National Center for Biotechnology in USA. Then, the PCR products were checked with single strand conformation polymorphism (SSCP) or with denaturing high performance liquid chromatography (DHPLC) technology, and then sequence analysis was performed on those with abnormal conformer or elution peak. Those discovered mutations were checked and located with the help from the website http://www.ncbi.nlm.nih.gov/. The results showed that we found some Heterozygotes, which means our design for the genetic researches on periodic paralyses with Chinese patients is available.PART TWO: Scanning SCN4A gene for mutations in Chinese families with hyperkalemic periodic paralysis or normokalemic periodic paralysis(1) Screening SCN4A gene for mutations in a Chinese family with hyperkalemic periodic paralysisIn this part, we aim to study the clinical features of hyperkalemic periodic paralysis (hyperKPP) and to confirm the relationship between SCN4A gene and hyperKPP with Chinese patients. The clinical features of 7 patients in a Chinese family with hyperKPP were summarized. All 24 exons of SCN4A gene were screened with DHPLC technology, and then sequence analysis was performed on those with abnormal elution peak. The Results were as follows: This family showed typical clinical features of hyperKPP without myotonia or paramyotonia. The progress of most patients was benign. Two mutations were foun...
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