远端型遗传性运动神经元病家系全基因组外显子测序研究  

Study of Exome Sequencing in a Distal Hereditary Motor Neuron Family

作　　者：师蕊婷[1] 周建文[2] 邓素雯 蒋嵩山[3] 何姝婧[1,4] 宋新明[1] 陈争[1] 

机构地区：[1]中山大学中山医学院医学遗传教研室,广东广州510080 [2]中山大学附属第一医院病理科,广东广州510080 [3]中山大学生命科学大学院,广东广州510006 [4]中山大学附属第六医院生殖医学研究中心,广东广州510655

出　　处：《中山大学学报（医学科学版）》2015年第2期209-214,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省科技计划项目(2010B031600039)

摘　　要：【目的】报告1例远端型遗传性运动神经元病(d HMN)家系,对家系进行分子遗传学研究,探寻致病基因,并探讨全基因组外显子测序在临床诊断和研究中的应用价值。【方法】对该家系进行临床及电生理检查,在排除与临床诊断相关已知基因的突变后,先对该家系的先证者和另一旁支的患者进行全基因组外显子测序、生物信息学分析,然后对采集到血样的22名家系成员,包括10例患者进行突变筛查及突变与疾病共分离分析。【结果】全基因组外显子测序、突变筛查及突变与疾病共分离分析结果显示该家系先证者和患者BSCL2基因3号外显子糖基化位点发生p.Ser90Leu突变,为国内首次报导。【结论】d HMN是一类临床和遗传异质性都很强的遗传病,外显子测序是诊断d HMN的有效方法。在研究具有高度遗传异质性的遗传病时,运用外显子组测序技术发现致病性突变比常规的PCR加产物测序更为简便、快速。【Objective】To report a Chinese family with distal hereditary motor neuropathy（d HMN）, to conduct molecular genetics study to identify the pathogenic gene and to explore the applications of exome sequencing in clinical diagnosis and research.【Methods】 Clinical and electrophysiological examination was performed, the proband and a collateral patient were subjected to exome sequencing, bioinformatics analysis, then the 22 family members whose blood sample were collected include 10 patients were subjected to co-segregation analysis by mutation screening. 【Results】 The results of exome sequencing and PCR sequencing showed that all patients have the mutation of glycosylation site in the 3rd exon of BSCL2 gene ： p.Ser90 Leu, which was first reported domesticly. 【Conclusion】 Our study confirms that exome sequencing is a comprehensive and feasible approach to diagnose d HMN. And for other high genetic heterogeneity diseases, exome sequencing is simpler and more convenient than normal PCR-direct sequencing.

关 键 词：全基因外显子组测序 远端型遗传性运动神经元病V型 BSCL2基因 

分 类 号：R394.3[医药卫生—医学遗传学]