摘要
目的探讨有镶边空泡远端肌病(DMRV)基因突变型。方法回顾性分析了中国DMRV一家系姐妹患者的临床、病理资料及其家系调查结果,对其GNE基因进行序列分析。结果一家系2代7人中有2例(均为第二代)发病,均为女性,青年晚期起病,首发症状为步态异常,四肢远端受累明显,股四头肌受累相对较轻;病情缓慢进展,发病后10年左右不能行走。主要病理改变为镶边空泡形成,肌浆或肌核内可见细丝状包涵体。2例患者突变位点相同,均为T1574C和C1943T复合杂合子突变,患者父亲携带单一C1943T点突变,其母亲和胞兄、胞姐均携带T1574C单一杂合子突变。结论中国DMRV一家系与日本人比较,其临床和病理改变一致。中国人DMRV患者也存在GNE基因复合杂合子突变,1574T→C为我们首次发现的致病性突变。
Objective To investigate the GNE gene mutation in 2 siblings with distal myopathy with rimmed vacuoles （DMRV） from a Chinese family. Methods Clinical manifestations and pathological findings as well as family histories were analyzed retrospectively. All the exons and their flanks of GNE gene were sequenced for detecting gene mutation. Results Among 7 nuinbers in 2 generations of the affected family, 2 siblings （all females） were diagnosed as having DMRV by their clinical manifestations and pathological findings in muscle biopsy. These 2 cases were first noticed of having gait disturbance in late adolescence. Distal muscle weakness and atrophy of the lower extremities, especially anterior tibial, was predominant in early stage. Proximal and trunk muscles were involved in the advanced stage. Quadriceps femoris were spared or slightly involved. The patients became non-ambulant about 10 years after the onset of the disease. The characteristic pathological findings were rimmed vacuoles formation in atrophic muscle fibers. Electronic microscopic study showed cytoplasmic and intranuclear filamentous inclusion bodies in degenerated fibers with rimmed vacuoles. Direct sequencing of GNE gene revealed that both patients had compound heterozygous mutations of a T to C substitution at np 1574 in exon 9 and a C to T at np 1943 in exon 11. Single C1943T mutation was found in her father, while her mother, sister and brother carried the T1574C mutation. Conclusions Chinese DMRV patients seem to develop similar clinical and pathological features as compared with those in Japanese. Compound heterozygous GNE gene mutations might be also found in Chinese family with DMRV. Our study described a new missense mutation（T1574C）in the GNE gene.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2005年第12期759-763,共5页
Chinese Journal of Neurology
基金
山东省优秀中青年科学家科研奖励基金资助项目(2004BS03007)
关键词
肌炎
包涵体
多酶复合物
活组织检查
突变
Myusitis, inclusion body
Multienzyme complexes
Biopsy
Mutation
