Kennedy病一家系的临床和分子遗传学  

Clinical and genetic study of Kennedy disease in a large Chinese family

作　　者：张社卿[1] 丁素菊[1] 郑惠民[1] 蒋德科[2] 李林国[2] 余龙[2] 

机构地区：[1]第二军医大学长海医院神经内科,上海200433 [2]复旦大学遗传工程国家重点实验室

出　　处：《中华神经科杂志》2006年第11期753-757,共5页Chinese Journal of Neurology

摘　　要：目的报道国内首例Kennedy病大家系,探讨其临床特征和分子机制。方法根据先证者的叙述对该家系4代74名个体进行家系调查,进行神经系统体检,常规检测神经电生理、肌电图、血清肌酸磷酸激酶(CPK)等。并经家族成员知情同意后抽取静脉血5ml,标准法抽取基因组DNA,聚合酶链反应(PCR)检测连接素基因(Cx32),证实无基因突变后再检测雄激素受体(AR)基因第一外显子CAG重复片段。结果经临床方法检出家系中另外3例患者,经AR基因检测,其CAG重复数均为50次;而先证者CAG重复数为51次;4例患者肌电图均显示感觉、运动神经受累及,血清CPK均增高;AR基因检测还发现1例症状前个体,其CAG重复数为50次。结论临床上Kennedy病多被误诊为多发性肌炎、肢带型肌营养不良,甚至Charcot-Marie-Tooth病等,AR基因检测是诊断本病最可靠的方法。Objective To report the first genetically proven Kennedy disease pedigree in China mainland in order to explore its clinical features and molecular mechanism and to heighten clinicians＇ awareness to the disease. Methods According to the clue given by the proband, a thorough survey was conducted over the pedigree including 74 individuals in 4 generations. Routine examination on nervous system, including nerve electrophysiology, electromyography was performed and serum CPK determined. After informed consent, venous blood was taken and genomic DNA was extracted by standard method. Connexin gene including its promoter region and its intron was sequenced and found normal. Then the CAG repeat region in the first exon of androgen receptor （AR） gene was amplified by PCR and sequenced directly. Results In the pedigree, other three individuals were clinically found to be ill with Kennedy disease and their CAG repeats numbers were 50, but the proband with 51 CAG repeats. Four patients＇ nerve electrophysiological study showed obvious sensory and motor involvement and their serum CPK values were elevated significantly. One presymptomatic individual, having 50 CAG repeats, was diagnosed as presymptomatic Kennedy disease by AR gene testing. Conclusions Clinically, Kennedy disease was easy to he misdiagnosed as polymyositis, limb-girdle muscular dystrophy, even Charcot-Marie-Tooth disease. AR gene testing is the most reliable diagnosing method.

关 键 词：肌萎缩 脊髓性 受体 雄激素 系谱 

分 类 号：R746[医药卫生—神经病学与精神病学]