家族性Creutzfeldt-Jakob病

Familial Creutzfeldt-Jakob disease

目的确定家族性Creutzfeldt-Jakob病(CJD)的临床特点并探讨其可能的发病机制。方法对一个CJD家系进行系谱调查,并采用蛋白捕获法进行脑脊液14-3-3蛋白定量;应用PCR方法,结合DNA测序技术,检测朊蛋白(PrP)基因类型。结果(1)两代4例的发病年龄早于散发性CJD,而且有早发的趋势;(2)先证者脑脊液14-3-3蛋白为125ng/ml,高出截点13.9倍;(3)先证者PRNP第788碱基和789碱基之间插入1个碱基A,致使PRNP第231位点发生插入突变;(4)患者弟弟及其女儿未发现有PrP基因突变。结论先证者为PRNP第231位点插入突变致家族性CJD,其临床表型与散发性CJD无明显不同,但发病年龄早于散发性CJD,同一家系患者死于同一年龄段。

Objective To identify the clinical characteristic of familial Creutzfeldt-Jakob disease （fCJD） in one pedigree with four cases in two-generation and to investigate its pathogenetic mechanism. Methods The pedigree was investigated in the fCJD kindred, protein capture assay was used to do quantitative analysis of 14-3-3 protein in the cerebrospinal fluid. Types of PrP gene mutation were studied by polymerase chain reaction （ PCR ） and DNA sequence analysis. Results （ 1 ） The onset age during four cases in two-generation was lower than the sporadic CJD and it tended to go down by generations. （2） The 14-3-3 protein level in the index case＇s cerebrospinal fluid was 125 ng/ml, which was higher than intersection point by 13.9 times. （3） In the index case, inserting mutation in site 231 of PRNP was induced by an adenine insertion between base 788 and 789. （4） No PrP gene mutation was found in the index case＇s younger brother and daughter. Conclusions The fCJD is identified in the index case, which is caused by inserting mutation in the site 231 of PRNP. There is no significant difference in the clinical manifestations between fCJD and sporadic CJD. However, the onset age of fCJD is lower than the sporadic CJD and patients from the same pedigree die at familiar ages.