TY -的T1的遗传障碍< em > MT-ATP6 < / em >导致轴突神经学疾病JF -神经学乔腓骨肌萎缩SP - 1145 LP - 1154 - 10.1212 / WNL。首页0 b013e3182698d8d六世非盟- 79 - 11 -罗伯特科学博士Pitceathly辛妮AU - m . Murphy AU -艾伦Cottenie盟安纳普尔纳峰Chalasani AU -玛丽·g·斯威尼盟凯茜伍德沃德AU - Ese大肠Mudanohwo盟伊恩•哈格里夫斯AU -西蒙·希尔AU -约翰土地非盟-贾尼斯·l·霍尔顿盟-亨利Houlden AU -朱利安·布莱克AU -迈克尔冠军非盟-弗朗西丝·弗林特AU -斯蒂芬妮·a·罗伯盟鲁珀特页面AU -迈克尔·罗斯盟杰奎琳宫非盟-卡罗尔·克罗盟谢丽尔朗文非盟-迈克尔·p·Lunn盟Shamima拉赫曼AU -玛丽·m·赖利盟迈克尔·g·汉娜Y1 - 2012/09/11 UR - //www.ez-admanager.com/content/79/11/1145.abstract N2 -目的:(CMT)腓骨肌萎缩症是最常见的遗传性神经肌肉紊乱,影响2500年1个人。首页线粒体DNA (mtDNA)突变一般不被认为是在简单遗传神经病变患者的鉴别诊断,尽管ATP对轴突的函数的基本要求。我们确定了mtDNA突变m.9185T> C在MT-ATP6 ATP6亚基编码的线粒体ATP合酶(OXPHOS复杂V)在homoplasmic水平在一个家庭与线粒体疾病严重的电机轴突神经病变是一个显著特征。这使我们假设突变2 mtDNA复杂V亚基编码基因,MT-ATP6 MT-ATP8,可能是一个未被孤立的轴突CMT和远端遗传性运动神经病变(dHMN)。方法:总共有442渊源者与CMT 2型(CMT2)(270)和dHMN(172)后被MT-ATP6/8突变筛查排除已知CMT2 / dHMN基因的突变。突变负载使用限制性内切核酸酶量化分析。Blue-native凝胶电泳(BN-PAGE)进行分析的影响m.9185T> C V在复杂的结构和功能。结果:三个进一步渊源者CMT2存在m.9185T> C突变。一些亲戚被列为dHMN。 Patients could be separated into 4 groups according to their mutant m.9185T>C levels. BN-PAGE demonstrated both impaired assembly and reduced activity of the complex V holoenzyme. Conclusions: We have shown that m.9185T>C in MT-ATP6 causes CMT2 in 1.1% of genetically undefined cases. This has important implications for diagnosis and genetic counseling. Recognition that mutations in MT-ATP6 cause CMT2 enhances current understanding of the pathogenic basis of axonal neuropathy. BN-PAGE=blue-native polyacrylamide gel electrophoresis; CMT=Charcot-Marie-Tooth; CMT2=Charcot-Marie-Tooth type 2; dHMN=distal hereditary motor neuropathy; LS=Leigh syndrome; mtDNA=mitochondrial DNA; NARP=neurogenic muscle weakness, ataxia, and retinitis pigmentosa; NCS=nerve conduction studies; OXPHOS=oxidative phosphorylation; UMN=upper motor neuron ER -