腓骨肌萎缩症MPZ基因突变筛查及其表型分析

发布时间：2018-02-14 15:47

本文关键词： 腓骨肌萎缩症突变筛查 CMT1B型 CMT2I/J型 MPZ 髓鞘蛋白零　出处：《中南大学》2014年硕士论文　论文类型：学位论文

【摘要】：背景及目的：腓骨肌萎缩症(Charcot-Marie-Tooth disease, CMT)是最为常见的遗传性周围神经病。其主要的临床表现为慢性进行性四肢远端肌无力及肌萎缩,常伴有感觉异常、弓形足、腱反射消失等。根据其电生理及病理特点,CMT分为脱髓鞘型(CMT1型)、轴索型(CMT2型)及中间型(intermediate CMT)。CMT是一种单基因遗传病,MPZ基因突变导致的CMT1B型约占CMT1型的5%,MPZ基因突变导致的CMT2I/J型大致占CMT2型的5%。此外,尚有MPZ基因突变导致中间型CMT (DI-CMTD)的报道。此课题针对近10多年来收集的70名CMT先证者进行MPZ基因突变筛查并对其临床表型进行归纳总结。方法：采用聚合酶链式反应结合DNA直接测序法对70名CMT先证者行MPZ基因突变检测。结果：1.我们发现4个家系及1例散发患者中4个不同的MPZ基因点突变,分别是：c.194CT, c.242AT, c.371CT, c.419CG。其中MPZ点突变c.242AT和c.419CG为新发突变,c.371CT为热点突变。2.新发突变c.242AT导致的CMT2I型患者表现为迟发型但进展快,而新发突变c.419CG导致的CMT1B型患者表现为相对迟发且进展缓慢。3.已知突变导致的CMT患者临床表现与既往报道大致相似,但2个热点突变(c.371CT)所致的CMT2型家系均无艾迪瞳孔及听力丧失表现。结论：1.中国CMT人群MPZ基因突变频率为4.35%,CMT1B型占所有CMT1型的3.08%,CMT2I型占所有CMT2型的6%。2.对于发病年龄较晚但进展速度较快且伴有严重感觉异常的CMT2型患者可优先开展MPZ基因突变筛查。3.对于发病年龄相对较晚但进展速度相对较慢的CMTl型患者可优先开展MPZ基因突变筛查。
[Abstract]:Background and purpose: CMT (Charcot-Marie-Tooth disease CMT) is the most common hereditary peripheral neuropathy. The main clinical manifestations of chronic progressive distal muscle weakness and muscle atrophy, often accompanied by abnormal sensation, arch foot, tendon reflexes. According to the electrophysiological and pathological characteristics, divided into CMT demyelinating type (CMT1 type), axonal type (type CMT2) and intermediate type (intermediate CMT.CMT) is a monogenic disease caused by mutations in the MPZ gene of CMT1B type about CMT1 type 5%, MPZ gene mutation type CMT2I/J to type CMT2 accounted for roughly 5%. in addition, there are mutations in the MPZ gene cause intermediate CMT (DI-CMTD) 70 CMT reports. This topic for the past 10 years collection of proband MPZ gene mutation screening and the clinical phenotypes are summarized.
Methods: polymerase chain reaction (PCR) combined with DNA direct sequencing was used to detect the mutation of MPZ gene in 70 CMT precursor.
Results: we found that 1. of 4 families and 1 sporadic patients in 4 different point mutations of MPZ gene, respectively is: c.194CT, c.242AT, c.371CT, c.419CG. and MPZ point mutations in c.242AT and c.419CG for new mutations, c.371CT is a hot spot mutation.2. new mutation type CMT2I patients showed c.242AT induced delayed onset but the rapid progress of the new mutation type CMT1B patients showed c.419CG caused relatively late and slow progress of known.3. mutations lead to the clinical manifestations of CMT patients had been reported were similar, but the 2 point mutations (c.371CT) CMT2 family by no Addie pupil and hearing loss.
Conclusion: 1. Chinese CMT population MPZ gene mutation frequency was 4.35%, CMT1B accounted for 3.08% of all CMT1 type, CMT2I type accounted for all types of CMT2 6%.2. for CMT2 patients with late onset ages but progress faster and severe abnormal sensation can give priority to the development of MPZ gene mutation screening of.3. in the age of onset is relatively late but CMTl patients progress slower can give priority to the development of MPZ gene mutation screening.

【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R746.4

【共引文献】