本文選題：家族性低鉀型周期性麻痹 + 離子通道　； 參考：《吉林大學》2014年碩士論文

【摘要】：實驗目的：隨著科技的發(fā)展，人們對疾病的認識逐漸深入，達到分子水平。離子通道病的概念走入人們的視線并逐漸被了解。家族性低鉀型周期性麻痹是最常見的離子通道病之一，它是一種常染色體顯性遺傳病，臨床上以骨骼肌反復發(fā)作弛緩性無力及發(fā)作時血清鉀降低為主要特征，通常由精神緊張、寒冷、感染、輸入葡萄糖溶液、體溫下降、代謝性堿中毒、麻醉以及應用類固醇藥物等誘發(fā)，給予補鉀治療后癥狀可基本消失。目前臨床上主要依據發(fā)病形式及發(fā)病時患者血清鉀濃度對該病進行診斷與治療。本實驗通過對一個家族性周期性麻痹家系成員進行基因序列分析探討其突變位點，研究其對臨床的指導意義。 材料與方法：實驗對象為目標家系同一代中的6名成員，其中3人患有低鉀型周期性麻痹，均為男性，發(fā)病形式基本相同，取其血樣提取出全基因組DNA。查閱相關文獻可知，家族性低鉀型周期性麻痹患者大約55%到70%左右是由骨骼肌電壓依賴性鈣通道CACNA1S基因突變所致，約8%到10%是由電壓門控性鈉通道SCN4A基因突變所致。在國內，主要有CACNA1S的R528G、R1239H、H916Q以及SCN4A的R672H/C基因突變型，分別存在于CACNA1S基因外顯子11、外顯子30及SCN4A外顯子12上。本實驗主要針對上述三段序列進行序列分析。根據CACNA1S外顯子11、30和SCN4A外顯子12序列的上下游內含子序列設計引物，利用PCR技術，獲得目的片段并進行體外擴增，最后對所獲得產物進行測序。通過家族中HOKPP患者基因序列與正常家族成員基因序列及正常人基因序列相比較，明確HOKPP患者是否存在基因突變以及基因突變類型。 結果：本實驗最終結果為未在此家族中成員中發(fā)現有CACNA1S基因及SCN4A基因突變。分析可能的原因如下：①家族成員中HOKPP患者均為散發(fā)病例；②在本實驗中，，僅對CACNAS1基因的30號外顯子、11號外顯子及SCN4A基因的12號外顯子進行測序，該家族成員中HOKPP患者可能存在其他基因型突變；③并不是所有的家族性HOKPP患者都存在有基因突變，目前約有20%家族性低鉀型周期性麻痹患者未能檢測到突變基因。
[Abstract]:Objective: with the development of science and technology, people's understanding of disease has gradually deepened and reached the molecular level. The concept of ion channel disease came into the eye and was gradually understood. Familial hypokalemic periodic paralysis is one of the most common ion channel diseases. It is an autosomal dominant disorder characterized by recurrent flaccid weakness in skeletal muscle and reduction of serum potassium during attack. Cold, infection, infusion of glucose solution, hypothermia, metabolic alkalosis, anaesthesia and steroid use, etc. At present, the diagnosis and treatment of the disease are mainly based on the form of the disease and the serum potassium concentration of the patients. In this study, the mutation site of a family member with familial periodic paralysis was analyzed by gene sequence analysis, and its clinical significance was studied. Materials and methods: the subjects were 6 members of the same generation of target families. Among them, 3 of them were suffering from hypokalemic periodic paralysis, all of them were male, the form of the disease was basically the same, and the whole genome DNA was extracted from their blood samples. About 55% to 70% of familial hypokalemic periodic paralysis patients were caused by CACNA1S gene mutation in skeletal muscle voltage-dependent calcium channel, and about 8% to 10% were caused by SCN4A gene mutation in voltage-gated sodium channel. In China, CACNA1S R528GN R1239H / H916Q and SCN4A R672H / C gene mutation were found in CACNA1S exon 11, exon 30 and SCN4A exon 12, respectively. The aim of this experiment is to analyze the sequence of the above three segments. Primers were designed according to the upstream and downstream intron sequences of CACNA1S exon 1130 and SCN4A exon 12. The target fragments were obtained by PCR and amplified in vitro. Finally, the obtained products were sequenced. By comparing the gene sequences of HOKPP patients with those of normal family members and normal individuals, we can find out whether or not there is gene mutation and the type of gene mutation in patients with HOKPP. Results: no mutation of CACNA1S gene and SCN4A gene was found in this family. In this study, exon 30, exon 11 and exon 12 of CACNAS1 gene and SCN4A gene were only sequenced. Not all patients with familial HOKPP had gene mutations, and about 20% of patients with familial hypokalemic periodic paralysis could not detect mutation genes.
【學位授予單位】：吉林大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R746.3

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