正常血钾型周期性麻痹与高钾型周期性麻痹关系的基因研究

Genetic study on the relationship between normokalemic periodic paralysis and hyperkalemic periodic paralysis

目的 探讨正常血钾型周期性麻痹 (normoPP)的临床特点并在基因水平上研究normoPP与高钾型周期性麻痹 (hyperPP)的关系。 方法 研究患有normoPP的 2个家系及 2例散发病例的临床特点 ,并应用聚合酶链反应 单链构象多态性分析 (PCR SSCP)方法检测其中 18例患者及其亲属的SCN4A基因 ,并对发现异常构象的单链进行测序。为了确保试验结果可靠 ,每个家庭中至少 1例患者进行了测序。结果 18例患者常规实验室检查未见异常 ,肌电图正常。散发病例 2在发作间期行肌肉活检 ,光镜下未见异常 ,电镜下示局灶性肌纤维变性。基因研究发现 :(1)家系 1发生Met15 92Val突变 ;(2 )散发病例 2及其父亲的SCN4A基因出现点突变G2 4 18A ,引起氨基酸序列的改变Val781Ile。 (3)家系 2和散发病例 1未发生已知的可导致hyperPP的突变 (Thr70 4Met、Ala115 6Thr、Met136 0Val、Ile14 95Phe、Met15 92Val)。结论 NormoPP与hyperPP在临床表现方面有一定的相似性 ,二者可有共同的突变位点。

Objective To discuss the clinical features of normokalemic periodic paralysis (normoPP) and try to clarify the associations between normoPP and hyperkalemic periodic paralysis (hyperPP).Methods Four unrelated families with 18 normoPP patients were analyzed to clinical features,and screened for previously known mutations of leading to hyperPP in SCN4A gene (Thr704Met,Ala1156Thr,Met1360Val,Ile1495Phe,Met1592Val) by PCR-based single-strand conformation polymorphism (PCR-SSCP) analysis.Sequence analysis of the aberrant conformer was performed,and at least one patient in every family were sequenced to ensure the reliability of the results.Results The laboratory tests were within normal ranges.Electromyograms and electrocardiograms were normal.One muscle biopsy was performed to the patient in family 4 after a brief attack of nomorPP.Examination by light microscopy showed no change,but by electronic microscopy showed occasionally degenerating myofibers.The results of genetic research were as follows: ① Met1592Val occurred in family 1; ②Val781Ile occurred in patient and her father of the family 4; ③ The patients in other families occurred with not the same mutations that had been found leading to hyperPP patients so far.Conclusions The similarity between normoPP and hyperPP might occur not only in clinical futures but also in genetic levels.