腓骨肌萎缩症Seipin、SH3TC2基因突变检测

发布时间：2018-03-09 13:09

本文选题：seipin　切入点：SH3TC2　出处：《中南大学》2014年硕士论文　论文类型：学位论文

【摘要】：背景和目的：腓骨肌萎缩症(Charcot-Marie-Tooth Disease, CMT)又称遗传性运动感觉性神经病(HMSN),是最常见的单基因遗传性周围神经病之一,发病率约1/2500。根据电生理和病理特征又可分为3型：CMT1型(脱髓鞘型)、CMT2型(轴突型)和CMT中间型。CMT具有高度的临床和遗传异质性,多个致病基因已被克隆。人类seipin基因又称Berardinelli-Seip先天性脂质营养不良基因(BSCL2), seipin基因突变引起的相关的运动神经元疾病被称之为"seipin病”,其中包括CMT2。SH3TC2基因突变可引起4C型CMT (CMT4C)和正中神经的单神经病。CMT4C是一类常染色体隐性遗传的脱髓鞘型CMT。本课题针对基因诊断未明确的CMT2型病人进行seipin基因突变筛查检测,同时对常染色体隐性遗传和散发的CMT病人进行SH3TC2基因突变筛查检测。方法：1.取50例临床表现、电生理或病理活检结果符合CMT2型诊断标准的患者行seipin基因PCR-直接测序筛查检测；2.取80例常染色体隐性遗传家系先证者(13例)和散发(67例)的CMT患者行SH3TC2基因PCR-直接测序筛查检测。结果：1.筛查出seipin基因一多态位点c.55GA；2.筛查出SH3TC2基因五个序列变异位点c.512GA、c.1402GT、c.283CG、 c.3143TC和c.3313GA.其中c.512GA、c.1402GT为多态位点而c.283CG、c.3143TC和c.3313GA暂未见报道。结论：1.CMT2型患者可以在筛查了常见CMT2型致病基因后进行seipin基因的点突变筛查,而隐性遗传家系先证者和散发病例在筛查了常见CMT致病基因以及常见隐性遗传致病基因后可以进一步进行SH3TC2致病基因的点突变检测；2.SH3TC2基因三个序列变异位点c.283CG、c.3143TC和c.3313GA暂未见报道的新发序列变异位点。图8幅,表9个,参考文献27篇
[Abstract]:Background and objective: Charcot-Marie-Tooth Disease (CMT), also known as hereditary motor sensory neuropathy (CMT), is one of the most common genetic peripheral neuropathy. The incidence rate is about 1 / 2 500. According to the electrophysiological and pathological characteristics, it can be divided into 3 types: CMT1 (demyelinating CMT2 (axonal type) and CMT intermediate type. CMT has high clinical and genetic heterogeneity. Several pathogenic genes have been cloned. Human seipin gene, also known as Berardinelli-Seip congenital lipid dystrophy gene BSCL2, seipin gene mutation caused by the associated motor neuron disease known as "seipin disease", including CMT2.SH3TC2 gene mutation can cause 4C type. CMT (CMT4C) and median nerve mononeuropathy. CMT4C is an autosomal recessive demyelinating CMT. In this study, seipin gene mutation screening was carried out in patients with CMT2 type whose gene diagnosis was not clear. The mutation of SH3TC2 gene in autosomal recessive and sporadic CMT patients was also detected. Methods 50 cases of clinical manifestations were taken. Patients with electrophysiological or pathological biopsy who met the diagnostic criteria of CMT2 type were screened for seipin gene PCR-direct sequencing. (13 patients with autosomal recessive genetic pedigree) and 67 patients with sporadic CMT were selected for SH3TC2 gene PCR-direct screening. Then sequenced the screening test. Results 1. The polymorphic loci of seipin gene c. 55GAN 2 were screened out. Five mutation loci of SH3TC2 gene, c.512GAAc. 1402GTC283CG, c. 3143TC and c.3313GA. were screened. Among them, c. 512GAAc. 1402GT was polymorphic, while c.283CGc.3143TC and c.3313GA were not reported. Conclusion: 1. CMT2 patients can be screened for point mutation of seipin gene after screening common CMT2 pathogenic genes. After screening common CMT pathogenic genes and common recessive genetic pathogenic genes, proband and sporadic cases of recessive genetic families can further detect the point mutations of SH3TC2 pathogenic genes. C. 3313GA not yet reported new sequence variation loci. Figure 8, Table 9, 27 references
【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

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