Gene Analysis Of The Hypokalemic Periodic Paralysis Pedigree

Objectives:The hypokalemic periodic paralysis including familial and sporadic hypokalemic periodic paralysis is an autosomal dominant skeletal muscle disease which is associated with ion channel abnormal function. It is characterized typically by episodic attacks of muscle weakness accompanied by decreasing levels of serum potassium. The symptoms improve rapidly after complement potassium. Severe symptoms are respiratory muscle paralysis, malignant arrhythmias, and even sudden death. Satiation, strenuous exercise, emotional stress and cold are inducing factors. Recent researches have shown that HOKPP is caused by mutations in the skeletal muscle ion channel CACNA1 S, SCN4 A and KCNE3 gene which encodes a1 subunit of the involtage-gated calcium, a subunit of sodium channel and subunit of potassium channel respectively. In the present study we analyzed gene mutations in CACNA1 S, SCN4 A and KCNE3 in this HOKPP pedigree. Methods:The experiment objects are six members in the hypokalemic periodic paralysis pedigree, three of them are patients, three of them are their immediate family members. They are all from the Chang Chun city, Jilin province and in the same pedigree. They are four males and two females.The forms of diseases are basically the same. Research statistics show, at present in China, there are mainly the following gene hotspot mutation: R528H/G, R897 S, R900G/S, R1239H/G of CACNA1 S, and R669 H, F671 S, R672H/G/C/S, P1158 S of SCN4 A, R83 H of KCNE3, which are on exon 11, exon 21,exon 30 of CACNA1 S and exon 12, exon 19 of SCN4 A, exon 1 of KCNE3 respectively. The sequence analysis of aforesaid six exons is conducted by PCR and DNA sequencing technology in this experiment. The main experimental steps include whole blood genome extraction, primer synthesis, PCR amplification gene, PCR product purification and DNA sequencing. Sequencing results are compared with the normal family members gene sequences and NCBI standard sequences to determine whether there is a mutation and gene mutation types. Results:The final results of this experiment indicate that no mutation in the gene CACNA1 S,SCN4A and KCNE3 was found in this pedigree. Conclusions:Firstly, the pathogenesis of HOKPP in this pedigree is another mutant gene or other sites of the aforementioned gene, which needs further study. Second, the patients in this pedigree may be sporadic cases. Combined with a large number of literature published, there are racial differences in the mutationed gene of HOKPP. The positive rate of mutation in Chinese populations is lower than that in Western populations. Third, not all HOKPP patients have gene mutation, no mutant gene is found in about 20% of hypokalaemic periodic paralysis patients at present. The etiology of the disease is not exact. Fourth, genetic analysis of the HOKPP pedigree can help clinical diagnosis and provide guidance for genetic counseling, prediction of disease and treatment.