CACNA1A基因的错义突变R1345Q导致一种新的共济失调伴随发作性全身震颤:临床特征、基因诊断及治疗的家系分析（英文

发布时间：2018-01-31 08:15

本文关键词： 共济失调 CACNAA 钙离子通道西比灵震颤　出处：《南方医科大学学报》2016年07期 　论文类型：期刊论文

【摘要】：目的 CACNA1A基因编码P/Q型钙离子通道的亚单位,它的突变至少造成3种等位基因病:发作性共济失调2型(EA-2)、家族性偏瘫性偏头痛1型(FHM1)和小脑脊髓共济失调6型(SCA 6)。本研究对一例19岁男性的发作性全身震颤患者的临床表现、基因分析结果和治疗效果进行研究。方法对病人及家系中有类似症状的成员进行专科查体;对先证者的DNA进行下一代测序分析以寻找致病基因,并用Sanger测序方法对家系成员进行基因变异的验证。结果神经专科查体显示患者共济失调体征,醉酒步态,头和躯干震颤。家系中另4个成员的症状和体征较轻。基因检测发现先证者携带有CACNA1A基因的杂合错义突变(NM_001127221.1 c.4034G-A,p.R1345Q,exon 25),为致病突变。家系中4个患病成员中也携带同样杂合突变。病人经醋甲唑胺治疗后效果不佳,但钙离子通道阻断剂西比灵治疗效果良好。结论根据患者的临床表现、基因突变类型和治疗效果,我们认为患者CACNA1A基因突变R1345Q所引起的疾病不属于EA2,FHM1,或SCA 6任何一种,而是一种新的伴有发作性震颤共济失调。
[Abstract]:Objective the CACNA1A gene encodes a subunit of P / Q type calcium channel, whose mutation causes at least three alleles: paroxysmal ataxia type 2 (AB-2). Familial hemiplegic migraine type 1 (FHM1) and cerebellar spinal cord ataxia type 6 (SCA6). This study was conducted in a 19-year-old male with paroxysmal systemic tremor. The results of gene analysis and therapeutic effect were studied. The DNA of the proband was sequenced in the next generation to search for the pathogenic gene. The genetic variation of family members was verified by Sanger sequencing. Results Neurophysical examination showed ataxia signs and drunken gait. Tremor of the head and trunk. Symptoms and signs of the other four members of the family were mild. Gene tests revealed that the proband carried a heterozygous missense mutation of the CACNA1A gene (. NM_001127221.1 c.4034G-A. P. R1345QFexon 25, which was a pathogenic mutation. The same heterozygous mutation was also carried in the 4 members of the family. The effect was not good after the treatment of oxazolamine. But the calcium channel blocker sibelium is effective. Conclusion according to the clinical manifestation, gene mutation type and therapeutic effect of calcium channel blocker. We believe that the disease caused by CACNA1A gene mutation R1345Q does not belong to EA2FHM1 or SCA 6, but is a new type of ataxia with paroxysmal tremor.
【作者单位】：南方医科大学南方医院神经内科;
【基金】：Supported by Guangdong Provincial Universities Fund(C1031243) Nanfang Hospital Fund for Experts Recruitment Program(17983)~~
【分类号】：R744.7
【正文快照】： INTRODUCTIONMutations in CACNA1A cause at least 3 allelic diseases,namely type 2 episodic ataxia(EA2,OMIM#108500),familial hemiplegic migraine type 1(FHM1,OMIM#141500)[1,2],and spinocerebellar ataxia type 6(SCA6,OMIM#183086)[3].The CACNA1A gene encodes t

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