CAJ | 학술논문

目的分析线粒体融合蛋白2(MFN2)基因在中国人腓骨肌萎缩症的突变情况,建立快速、有效和经济的基因诊断方法 .方法应用变性高效液相色谱(DHPLC)结合DNA直接测序的方法 ,对9个常染色体显性遗传的CMT2先证者和26个散发CMT2病例共35例患者进行MFN2基因编码区17个外显子及其侧翼区的突变检测.结果在35例腓骨肌萎缩症患者中共检测到3种MFN2基因序列变异:c.281G→A,c.395G→A和c.408A→T,其中c.395G→A(C132T)为首次报道的致病突变,c.281G→A(R94Q)为已知致病热点突变,c.408A→T(V136V)为单核苷酸多态.DHPLC突变检测的敏感性和特异性为100%.结论首次在国内应用DHPLC结合DNA直接测序对MFN2基因进行突变检测,发现2个致病突变和1个单核苷酸多态.DHPLC结合DNA直接测序法可准确有效地用于大规模MFN2基因突变筛查.
목적 분석선립체융합단백2(MFN2)기인재중국인비골기위축증적돌변정황,건립쾌속、유효화경제적기인진단방법 .방법 응용변성고효액상색보(DHPLC)결합DNA직접측서적방법 ,대9개상염색체현성유전적CMT2선증자화26개산발CMT2병례공35례환자진행MFN2기인편마구17개외현자급기측익구적돌변검측.결과 재35례비골기위축증환자중공검측도3충MFN2기인서렬변이:c.281G→A,c.395G→A화c.408A→T,기중c.395G→A(C132T)위수차보도적치병돌변,c.281G→A(R94Q)위이지치병열점돌변,c.408A→T(V136V)위단핵감산다태.DHPLC돌변검측적민감성화특이성위100%.결론 수차재국내응용DHPLC결합DNA직접측서대MFN2기인진행돌변검측,발현2개치병돌변화1개단핵감산다태.DHPLC결합DNA직접측서법가준학유효지용우대규모MFN2기인돌변사사.
Objective To analyze MFN2 gene mutation in Chinese patients Charcot-Marie-Tooth disease (CMT) and to establish a quick and effective diagnostic method. Methods Through denaturing high-performance liquid chromatography (DHPLC) combined with DNA sequencing, MFN2 gene mutation analysis was carried out in 35 Chinese CMT2 patients including 9 probands of CMT2 pedigree and 26 sporadic CMT2 patients. Results The investigators found three abnormal sequence variations in MFN2 gene:c. 281G→A,c. 395G→A and c. 408A→T. c. 395G→A ( C132T) was a novel causative missense mutation firstly reported while c. 281G→A ( R94Q) a hotspot mutation and c. 408A→T( V136V) a single nucleotide polymorphism (SNP). The accuracy and specificity of DHPLC detection reached up to 100%. Conclusion Through DHPLC combined with DNA sequencing, MFN2 mutations are detected in Chinese CMT2 patients. There are two causative missense mutations; c. 395G→A (C132T) and c. 281G→A (R94Q) and one SNP c. 408A→T (V136V). Such a method is an effective and economic diagnostic screening tool of MFN2 gene in CMT patients on a large scale.