CAJ | 학술논문

目的分析伴有短暂可逆性脑白质病变的X连锁显性夏科-马里-图斯病(CMTX1)患者临床和头颅核磁(MRI)特点及可能的发生机制,探讨GJB1基因型与患者脑白质病变的相关关系.方法以临床诊断为CMTX1且伴短暂可逆性脑白质病变的3个先证者及其家庭成员为研究对象,对其进行GJB1基因检测分析.并收集国际已报道的16例患者,对连同本研究3例共19例进行临床特征及突变类型的总结分析.结果 3例先证者均发现GJB1基因编码区的错义突变.19例伴短暂可逆性脑白质病变的CMXT1患者发作期表现为:四肢无力、构音障碍、吞咽困难等,无意识障碍及惊厥；平均发作持续时间13 h(10 min～72 h),发作均可自行完全缓解；9例病程中有多次发作；发作期头颅MRI表现为脑室周围白质对称性长T1、长T2、Flair高信号,DWI高信号,后头部显著,常累及胼胝体压部,发作期及发作后1周内脑白质异常最为明显,1个月明显好转,4～6个月完全恢复.发生可逆性脑白质病变的CMTX1患者的突变位点在GJB1蛋白上无特定分布区域.结论少数CMTX1患者可出现短暂可逆性的脑白质病变,推测可能与细胞间通道功能障碍导致胶质细胞一过性水肿有关.GJB1基因型与患者是否出现脑白质病变临床表型无明确相关性.
목적 분석반유단잠가역성뇌백질병변적X련쇄현성하과-마리-도사병(CMTX1)환자림상화두로핵자(MRI)특점급가능적발생궤제,탐토GJB1기인형여환자뇌백질병변적상관관계.방법 이림상진단위CMTX1차반단잠가역성뇌백질병변적3개선증자급기가정성원위연구대상,대기진행GJB1기인검측분석.병수집국제이보도적16례환자,대련동본연구3례공19례진행림상특정급돌변류형적총결분석.결과 3례선증자균발현GJB1기인편마구적착의돌변.19례반단잠가역성뇌백질병변적CMXT1환자발작기표현위:사지무력、구음장애、탄인곤난등,무의식장애급량궐；평균발작지속시간13 h(10 min～72 h),발작균가자행완전완해；9례병정중유다차발작；발작기두로MRI표현위뇌실주위백질대칭성장T1、장T2、Flair고신호,DWI고신호,후두부현저,상루급변지체압부,발작기급발작후1주내뇌백질이상최위명현,1개월명현호전,4～6개월완전회복.발생가역성뇌백질병변적CMTX1환자적돌변위점재GJB1단백상무특정분포구역.결론 소수CMTX1환자가출현단잠가역성적뇌백질병변,추측가능여세포간통도공능장애도치효질세포일과성수종유관.GJB1기인형여환자시부출현뇌백질병변림상표형무명학상관성.
Objective To analyze the phenotype and genotype of CMTX1 patients with episodic transient reversible white matter involvement,and delineate the features of brain MRI in the episode and the possible mechanisms.Method Three Chinese probands and their family members were sequenced in the coding regions of GJB1.With the other 16 reported CMTX1 patients with episodic transient reversible white matter involvement,the clinical feature of the episodic central nervous system symptoms and the genotypes were reviewed.Result Missense mutations in GJB1 were identified in all 3 probands.In 19 patients with transient reversible white matter involvement,the episodes were manifested as weakness of the limbs,dysarthria,and dysphagia,without disturbance of consciousness or seizures.The episodes lasted for 13 hours (10 min-72 hours) with complete remission in all patients; There were multiple episodes in 9 patients.During the episode,brain MRI showed symmetrical high signals in T2 weighted,Flair and DWI images in periventricular white matter,with predominance in posterior region including splenium of corpus callosum.These changes in imaging were most prominent during or within 1 week after the clinical episode.Significant improvements occurred within 1 month,with complete remission within 4-6 months.No specific locations of mutant amino acids in GJB1 protein were found in these patients with episodic transient reversible white matter involvement.Conclusion Episodic transient reversible white matter involvement may present in a small number of patients with CMTX1.Transient edema of oligodendrocytes due to the dysfunction of gap junction may be involved in the pathogenesis.There is no correlation between the location of the mutant amino acids in GJB1 and the occurrence of the episodes.