8例肢带型线粒体肌病患者的临床、病理特点和线粒体基因突变分析  

The clinical, pathological features and analysis of mitochondrial DNA mutation in 8 cases with limb-girdle mitochondrial myopathy

作　　者：赵丹华[1] 栾兴华[1] 陈彬[1] 洪道俊[1] 张秋荣[1] 张巍[1] 吴士文[2] 袁云[1] 王朝霞[1] 

机构地区：[1]北京大学第一医院神经内科,100034 [2]武警总医院神经内科,100039

出　　处：《中国神经免疫学和神经病学杂志》2010年第5期334-337,共4页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家自然科学基金资助项目(No.30870864)

摘　　要：目的分析肢带型线粒体肌病患者的临床、病理特点及线粒体基因突变情况。方法回顾分析8例肢带型线粒体肌病患者的临床特征及肌肉病理改变,并进行线粒体DNA(mtDNA)突变分析。结果 8例患者发病年龄为5～30岁,病程2～36年,主要表现为四肢近端肌无力和运动耐力下降,仅1例有双下肢肌痛。血肌酸激酶水平呈轻中度升高。电生理检查结果最示骨骼肌呈肌源性或神经源性损害。骨骼肌病理检查结果显示所有患者存在破碎红纤维(RRF),细胞色素C氧化酶染色可见深染的RRF,也可见阴性的RRF。4例患者存在tRNAleu^(UUR)A3243G突变,1例为tRNAlys A8344G突变,1例同时存在tRNAleu^(UUR)A3276G和ATP酶6编码基因G9196A(D224N)突变,1例为细胞色素b编码基因G15221A(D159N)突变,1例则为细胞色素C氧化酶亚单位Ⅲ的编码基因A9567G(I121V)突变。结论肢带型线粒体肌病主要表现为四肢肌无力和运动耐力下降。骨骼肌病理改变存在一定的异质性。mtDNA的tRNA基因可能是家族性肢带型线粒体肌病的热点突变区。Objective To describe the clinical and myopathological features of 8 patients with limbgirdle mitochondrial myopathy as well as the results of mitochondrial DNA mutation analysis. Methods Clinical manifestations and myopathological features were retrospectively evaluated in 8 patients with limb-girdle mitochondrial myopathy. Mitochondrial DNA mutation analysis was performed in all the patients. Results Eight patients, with onset age ranging from 5 to 30 years old, had a clinical course from 2 to 36 years. The main clinical features were proximal muscle weakness of limbs and exercise intolerance. Only 1 patient had myalgia in lower limbs. Laboratory examination revealed mild to moderate elevation of serum creatine kinase. There were myogenic or neurogenic changes of skeletal muscle on electromyography in some of them. Ragged-red fibers （RRFs） were shown in biopsies skeletal muscle in all the patients. Either positive or negative RRFs could be detected on cytoehrome c oxidase （COX） staining. Molecular analysis of mitochoudrial DNA indicated tRNAleu（UUR） A3243G mutation in 4 cases, tRNAlys A8344G mutation in 1, tRNAleu（UUR） A3276G and ATPase 6 coding gene G9196A （D224N） mutation in 1, cytochrome b （CYTB） coding gene G15221A （D159N） mutation in 1 and cytochrome c oxidase subunit Ⅲ （COⅢ） coding gene A9567G （I121V） mutation in 1 case. Conclusions The main manifestations of limb-girdle mitochondrial myopathy were muscle weakness of limbs and exercise intolerance. There existed heterogeneity in both the myopathological changes and causative mutations. Mitochondrial tRNA mutations may be the hot spot zone for familial limb-girdle mitochondrial myopathy.

关 键 词：肢带型线粒体肌病 破碎红纤维 细胞色素C氧化酶 TRNA基因 

分 类 号：R746.9[医药卫生—神经病学与精神病学]