Analysis Of Mutation In Gene CACNA1S And SCN4A Of The Hypokalemic Periodic Paralysis Pedigree

Background Representative disease in the metastatic hypokalemic periodic paralysisis the primary hypokalemic periodic paralysis, including familial hypokalemic periodicparalysis and sporadic hypokalemic periodic paralysis, and secondary hyperthyroidismthyrotoxic hypokalemic periodic paralysis which is referred to as THOKPP. THOKPP，the main type in China, is induced by high Hypothyroxinemia.The age of onset of20-40years, approximately13%of male patients with hyperthyroidism disease inChina and other East Asian countries undergo the THOKPP, and the ages of onset areusual20-40years. The primary hypokalemic periodic paralysis is an autosomaldominant hereditary muscle disease. They are similar in clinical characteristics, suchas,suddenly onset of hypokalemia,muscle weakness, severe respiratory muscleparalysis, malignant arrhythmias, and even sudden death. It often occurs afterstrenuous exercise, a large number of high-carbohydrate diet, alcohol consumption,emotional stress or cold factors, and K+in the extracellular suddenly transferred to thecells leads to hypokalemia and muscle paralysis. Recent genetic, molecular biologicand electrophysiological combination researches have shown that HOKPP is due tomutations in the skeletal muscle ion channel CACNA1S, SCN4A or KCNE3gene(which coding involtage-gated calcium a1subunit, sodium a subunit or potassiumchannel subunit respectively).HOKPP linked to CACNA1S matutations was definedas type I, and linked to SCN4A mutations was difined as type II. In the literaturesreported, about69%was type I, and about8.6%was type II, and22.4%had noidentified mutation. HOKPP haves not only gene heterogeneity, but also phenotypeheterogeneity. At present, the mechanism of mutations in the disease is unknown.what’s more, the characters in Chinese pedigree are scattered, less mutation sites and cases reported, comparing with Western Caucasian. There is a relatively completemolecular epidemiological data formed.Objective We collected three new pedigrees on the basis of our previous study, andinvestigate the gene CACNA1S and SCN4A in hypokalemic periodic paralysis(HOKPP), and compare with gene mutated status in Western Caucasian HOKPPpatients reported in the literature of previously and analysis the characteristics of themutation point. By means of that, we can summarize the regularity of the molecularepidemiology of the disease. At the same time it learn explore hypokalemic periodicparalysis pathogenesis and study of THOKPP and Provide references by combinedwith the ongoing animal experiments.Methods To define whether the presence of the gene mutation, genetic sequencingin order of common mutation site, a rare mutation site and the other exon of notmutated for CACNA1S and SCN4A were finished in the two Familial HOKPPpedigree, the one Thyrotoxic HOKPP pedigree and4Sporadic HOKPP by PCR andDNA sequencing technology, which were compared with gene library referencedsequence.We collected nine relevant literature about the gene CACNA1S and SCN4Amutation of HOKPP pedigree published from January1999to December2012in thePubMed database.Results Paroxysmal proximal limb weakness, weakened tendon reflexes whichtypical symptoms of the HOKPP in patients. Auxiliary examination confirmed lowerserum potassium, electrocardiogram (ECG) showed hypokalemic.Results above werein accordance with clinical diagnosis of HOKPP. Gene analysis showed no mutationsin the the gene CACNA1S and SCN4A of the proband and family members in the three HOKPP pedigree, and four patients of Sporadic HOKPP. The literature reportedpreviously showed that mutation positive rate is much higher than Chinese populationin the gene CACN1AS and SCN4A in HOKPP in patients of the Western Caucasian.That is consistent with the report of other Chinese scholars.Conclusion Firstly, mutation rate is lower in the gene CACN1AS and SCN4A in theChinese HOKPP patients, which is lower than the results of Western Caucasianpatients obviously. Second, the reasons that the gene CACNA1S and SCN4A in theChinese mutation-positive rate is far lower than the Western Caucasians are racialdifferences in the mutationed gene of patients in the Chinese and Western Caucasian.Inaddition to the mutant gene reported,there are also other virulence genes in the Chinese.Therefore, in addition to screening for known mutated gene, we are also need to screenother gene which the most related with K~+closely in future research, promoting thestudy of the HOKPP.