一个正常血钾型周期性瘫痪家系临床及分子遗传学研究  被引量:2

Clinical and molecular genetic analysis of a family with normokalemic periodic paralysis

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作  者:魏翠洁[1] 王硕[1] 焦辉[1] 熊晖[1] 洪道俊[2] 汪东[3] 蒲利华[3] 

机构地区:[1]北京大学第一医院儿科,100034 [2]北京大学第一医院神经内科,100034 [3]西安市儿童医院神经内科

出  处:《中华儿科杂志》2013年第1期47-51,共5页Chinese Journal of Pediatrics

基  金:北京市自然科学基金(7112133)

摘  要:目的探讨一个家族性正常血钾型周期性瘫痪家系的临床特点,并检测其致病基因SCN4A的突变情况。方法对先证者及家系成员的临床资料进行总结,明确临床特点。提取家系成员的外周血基因组DNA,PCR反应扩增骨骼肌钠通道SCN4A基因的外显子后直接测序,确定基因突变的类型。并回顾总结既往文献中正常血钾型周期性瘫痪家系的临床表现及基因突变情况。结果家系中15例患者临床上符合正常血钾型周期性瘫痪的诊断标准,突出特点为:婴儿期起病,反复发作的骨骼肌迟缓性瘫痪,很快自行恢复,发作期血钾正常,发病与饥饿、寒冷、高温、久坐不动、剧烈运动、进食香蕉葡萄等高钾饮食有关,病程长者存在缓慢进展性肌病,智力不受影响,其中4例肌活检病理表现为肌营养不良改变。家系中12例患者进行候选基因SCNdA突变检测,均证实存在c.2111T,这是一个已知致病突变,且为热点突变,而9名无症状家系成员未发现该突变。家系中代代发病,且男女均受累,符合常染色体显性遗传的规律。结论确诊了一个SCN4A基因突变所致的正常血钾型周期性瘫痪家系,明确了该家系中的致病基因突变,为该家庭进行产前诊断提供了可能。Objective Periodic paralysis (PP) is one type of skeletal muscle channelopathies characterized by episodic attacks of weakness. It is usually classified into hyperkalemic periodic paralysis (HyperPP), hypokalemic periodic paralysis (HypoPP) and normokalemic periodic paralysis (NormoPP) based on the blood potassium levels. HypoPP is the most common type of these three and NormoPP is the rarest one. The aim of this study was to explore the clinical and genetic features of a Chinese family with normokalemic periodic paralysis (NormoKPP). Method Clinical features of all patients in the family with NormoKPP were analyzed. Genomie DNA was extracted from peripheral blood leukocytes and amplified with PCR. We screened all 24 exons of SCN4A gene and then sequence analysis was performed in those who showed heteroduplex as compared with unaffected controls. Result ( 1 ) Fifteen members of the family were clinically diagnosed NormoKPP, and their common features are: onset within infacy, episodic attacks of weakness, the blood potassium levels were within normal ranges, high sodium diet or large dosage of normal saline could attenuate the symptom. One muscle biopsy was performed and examination of light and electronic microscopy showed occasionally degenerating myofibers. (2) Gene of 12 patients were screened and confirmed mutations of SCN4A genes--c. 2111 T 〉 C /p. Thr704Met. Conclusion The study further defined the clinical features of patients with NormoKPP, and molecular genetic analysis found SCN4A gene c. 2111 T 〉 C/p. Thr704Met point mutation contributed to the disease. In line with the autosomal dominant inheritance laws, this family can be diagnosed with periodic paralysis, and be provided with genetic counseling. And the study may also help the clinical diagnosis, guide treatment and genetic counseling of this rare disease in China.

关 键 词:离子通道病 常染色体显性 正常血钾型周期性瘫痪 

分 类 号:R746.3[医药卫生—神经病学与精神病学]

 

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