CAJ | 학술논문

目的报道6个X连锁Charcot-Marie-Tooth病1型(CMTX1)家系的神经病理和基因型改变特点.方法 6个CMTX1家系的先证者均为男性,发病年龄11 ～24岁,出现下肢远端为主的肌无力、腱反射减低和轻度感觉减退.先证者1伴随发作性白质脑病,先证者5伴随小脑性共济失调.12名家系成员也出现周围神经损害症状,另7名存在高弓足或腱反射减低.对6例先证者行腓肠神经活体组织检查,并对6例先证者、8名受累家庭成员和10名无症状家系成员及50名健康女性进行缝隙连接蛋白32( Cx32)基因测序.结果 6例先证者有髓神经纤维出现轻-中度减少伴轴索再生变性,5例出现薄髓鞘神经纤维,其中3例伴洋葱球样结构,2例伴炎细胞浸润.6个家系的Cx32基因存在5种新突变和1种同义突变,即L20T、I127F、D178G、A197V错义突变,403_404T insT插入突变和L10L沉默突变,10名无症状家系成员中有4名女性为携带者,6名男性和健康对照均没有这些基因突变.结论该组CMTX1患者的周围神经病理改变以慢性轴索损害为主,Cx32基因较多新突变的出现提示我国CMTX1患者具有个体突变特点.
목적 보도6개X련쇄Charcot-Marie-Tooth병1형(CMTX1)가계적신경병리화기인형개변특점.방법 6개CMTX1가계적선증자균위남성,발병년령11 ～24세,출현하지원단위주적기무력、건반사감저화경도감각감퇴.선증자1반수발작성백질뇌병,선증자5반수소뇌성공제실조.12명가계성원야출현주위신경손해증상,령7명존재고궁족혹건반사감저.대6례선증자행비장신경활체조직검사,병대6례선증자、8명수루가정성원화10명무증상가계성원급50명건강녀성진행봉극련접단백32( Cx32)기인측서.결과 6례선증자유수신경섬유출현경-중도감소반축색재생변성,5례출현박수초신경섬유,기중3례반양총구양결구,2례반염세포침윤.6개가계적Cx32기인존재5충신돌변화1충동의돌변,즉L20T、I127F、D178G、A197V착의돌변,403_404T insT삽입돌변화L10L침묵돌변,10명무증상가계성원중유4명녀성위휴대자,6명남성화건강대조균몰유저사기인돌변.결론 해조CMTX1환자적주위신경병리개변이만성축색손해위주,Cx32기인교다신돌변적출현제시아국CMTX1환자구유개체돌변특점.
Objectives To report pathological and genetic features of 6 Chinese families with Xlinked Charcot-Marie-Tooth disease type 1 ( CMTX1 ).Methods The index cases from 6 families with CMTX1 are males with onset of disease between 11 and 24 years old.All of them had distal leg muscle weakness,accompanied with areflexia and sensory loss in the feet.Additionally,the index 1 presented with recurrent encephalopathy and the index case 5 with cerebellar ataxia.Peripheral neuropathy was found in 12 family members,while other 7 members showed talipescavus and hyporeflexia.Sural nerve biopsies were performed in all index cases.Connexin 32(Cx32) gene was analyzed in the index cases,8 affected and 10unaffected family members as well as 50 healthy women control subjects.Results Mild to moderate loss of myelinated fiber with axonal degeneration and regeneration clusters were found in all index cases. Thin myelin fibers were found in 5,small onion bulbs in 3 and inflammatory infiltrates in 2.Five novel mutations (I20T,I127F,D178G,A197V,403_404insT) and one L10L synonymous mutation were detected in the 6index cases and their affected family members.The same mutations,in heterozygous state,were detected in 4 female family members without clinical symptoms,but not found in 6 male unaffected family members.The same mutations were not found in healthy control subjects.Conclusions The CMTX1 patients in our study present predominantly axonal lesions.Frequent novel Cx32 gene mutations indicated that private mutations may be common in Chinese CMTX1 patients.