CAJ | 학술논문

目的报道一个早发型夏科-马里-图斯病(CMT)2A2家系,探讨其临床和病理特点.方法该家系共有5例患者,呈常染色体显性遗传,先证者为36岁女性,6岁开始出现下肢进行性无力,8岁出现双足内翻.家族中另有2例男性和2例女性发病,发病年龄3～7岁,主要表现为缓慢进展的四肢远端肌肉无力、萎缩,伴随四肢远端感觉减退、腱反射减退及关节挛缩.先证者和其儿子的上肢感觉神经、下肢感觉和运动神经诱发电位波幅不能引出.对先证者左侧腓肠神经进行活体组织病理检查.对先证者和其他4例家系患者、3名无症状家系成员行MFN2基因测序.结果病理检查可见腓肠神经有髓纤维数目重度减少,以大有髓神经纤维减少为主,伴随个别有髓神经纤维再生簇结构以及不典型的洋葱球样结构.电镜下可见轴索中线粒体聚集,未发现线粒体结构异常.5例患者存在MFN2基因R94W突变,无症状家系成员无此突变.结论我国存在早发型CMT2A2家系,患者周围神经缺乏有髓神经纤维再生改变,提示MFN2基因突变对神经元的损害更大.
목적 보도일개조발형하과-마리-도사병(CMT)2A2가계,탐토기림상화병리특점.방법 해가계공유5례환자,정상염색체현성유전,선증자위36세녀성,6세개시출현하지진행성무력,8세출현쌍족내번.가족중령유2례남성화2례녀성발병,발병년령3～7세,주요표현위완만진전적사지원단기육무력、위축,반수사지원단감각감퇴、건반사감퇴급관절련축.선증자화기인자적상지감각신경、하지감각화운동신경유발전위파폭불능인출.대선증자좌측비장신경진행활체조직병리검사.대선증자화기타4례가계환자、3명무증상가계성원행MFN2기인측서.결과 병리검사가견비장신경유수섬유수목중도감소,이대유수신경섬유감소위주,반수개별유수신경섬유재생족결구이급불전형적양총구양결구.전경하가견축색중선립체취집,미발현선립체결구이상.5례환자존재MFN2기인R94W돌변,무증상가계성원무차돌변.결론 아국존재조발형CMT2A2가계,환자주위신경결핍유수신경섬유재생개변,제시MFN2기인돌변대신경원적손해경대.
Objective To report clinical and pathological features in a Chinese family with CharcotMarie-Tooth disease type 2A2 (CMT2A2). Methods There were 5 patients (2 male and 3 female) in a family with an autosomal dominant inheritance pattern. The index case was a 36 years old woman. She developed progressive distal limb weakness at the age of 6, with pescavus at the age of 8. Other 4 family members presented with similar symptoms between the age of 3-7. Physical examination showed distal limb weakness and wasting, loss of sensory and contracture in all of them. Nerve conduction velocity revealed non-potential in several motor and sensory nerves in the proband and her son. Sural nerve biopsy was performed on the proband. The sequence of MFN2 gene was analyzed in DNA from 5 patients and 3 asymptomatic members. Results Sural nerve biopsy revealed severe loss of myelinated fibers with few regenerating clusters. Electron microscopy revealed aggregation of mitochondrian in the axons. A R94W mutation in MFN2 gene has been identified in 5 patients, but not in unaffected members. Conclusions We confirmed Chinese CMT2A2. Absent of regenerating cluster in the nerve indicated that MFN2 mutation predominantly resulted in lesions in the neurons.