Machado－Joseph病基因CAG重复数目与临床相关性  

Andysisof(CAG)narrayinMJD1geneofMachado┐Josephdiseaseanditsclinicalcorrelations

作　　者：周永兴[1,2] 王国相[1,2] 范慕贞[1,2] 陈志华[1,2] 李玉芬[1,2] 周联生 孙逸平[1,2] 周宝玉 刘兴洲[1,2] 杨秉贤 

机构地区：[1]中日友好医院神经内科 [2]中日友好临床医学研究所生化室

出　　处：《中华神经科杂志》1996年第6期357-360,共4页Chinese Journal of Neurology

基　　金：国家自然科学基金;卫生部课题基金;日本JICA资助

摘　　要：为了探讨Ｍａｃｈａｄｏ－Ｊｏｓｅｐｈ病（ＭＪＤ）的发病机理，分析了来自４个家系的６１名成员及１８名健康人的基因（ｃｙｔｏｓｉｎｅａｄｅｎｉｎｅｇｕａｎｉｎｅ，ＣＡＧ）重复数目后，发现所有１５例患者均存在ＣＡＧ重复扩展，其重复数目为７２～８６。正常人ＣＡＧ重复数目为１４～４０，两者之间差异有显著意义。另外，发现发病年龄与ＣＡＧ重复数目呈明显的负相关。２例发病年龄为５岁和１１岁的青少年患者，ＣＡＧ重复数目分别为８６和８３，大于所有成年发病的患者，且病情进展快，症状严重。临床症状与ＣＡＧ重复数目无明显相关性。进一步分析家系各代ＣＡＧ重复数目时，发现ＣＡＧ重复数目存在代间不稳定。Machado-Josephdisease(MJD)isanautosomaldominant,multisystem,neurodegen-erativedisorderassociatedwiththeexpansionofacytosineadenineguanine(CAG)trinucleotidere-peatintheMJD1gene.Thesizeofthe(CAG)narraywasanalyzedfor61samplesfrom4ChineseMJDfamiliesand18Chinesenormalcontrols.The(CAG)narrayin15MJDchromosomeswasex-pandedto72～86,and14～40innormalchromosomes.TheCAGrepeatnumbersofnon-afectedin-dividualsclearlydistinguishedfromtherangeinafectedpatients.Therewerenosubjectswithinter-mediatesizebetweenthenormalandaffectedgroups.Futhermore,thesignificantnegativecorrela-tionwasnotedbetweentheageattheonsetofthesymptomsandtheCAGrepeatlengths.Twojuve-nilepatientswiththeagesofonsetat5and11yearsshowedlargenumbersofCAGrepeatunits(86and83,respectively).Theyhadlargerexpansionsofthe(CAG)narraythanthoseofaloftheadult-onsetcases.Themajorclinicalfeaturessuchascerebelarataxia,pyramidalsigns,extrapyami-dalsigns,amyotrophyandprogressiveexternalophthalmoplegiawerenotcorrelatedwithCAGre-peatlengths.TheintergenerationalchangesofCAGrepeatsinMJDwereunstable,andthisinstabili-tywasconsideredthemolecularbasisoftheclinicalphenomenonofanticipation.

关 键 词：M-J病 Mchado-Joseph CAG重复序列 病理 

分 类 号：R741.02[医药卫生—神经病学与精神病学] R596.1[医药卫生—临床医学]