遗传性CJD一家系随访分析

Follow-up of a pedigree of familial Creutzfeldt-Jakob disease

目的随访一个遗传性朊蛋白病的家系,对全部家系成员进行朊蛋白基因(PRNP)突变的筛查,探讨患病者的表型和突变发生率。方法研究对象包括28例家系成员和310例健康对照。对研究对象的PRNP基因的开放阅读框架进行PCR扩增,产物直接测序,异常者重复测序,并与对照组对比。收集新发病例的影像和神经电生理资料。结果共发现15例G114V基因突变者,其中3例发病,12例为携带者。1例新发病的患者表现为进行性痴呆、肌阵挛、帕金森综合征,头颅MRI示左侧颞叶轻度萎缩,脑电图有典型的周期性放电。结论本家系为常染色体显性遗传的家族性CJD,新发病例的出现进一步明确了这一表型诊断,部分携带者不发病提示存在不完全外显。

Objective To detect the PRNP gene mutations in a pedigree of familial Creutzfeldt-Jakob disease and evaluate the mutation rate of PRNP gene and the phenotype of the affected members. Methods The study group consisted of 28 members of a familial dementia pedigree and 310 healthy subjects. Genomie DNA was extracted from peripheral blood leucocytes of all subjects followed by in vitro amplification using polymerase chain reaction （PCR）. The PCR products were directly sequenced by Sanger method. Result We detected missense mutations of PRNP gene in 15 family members, in which 3 were patients and 12 were healthy carriers, resulting in G114V mutation in the prion protein. A new patient demonstrated progressive dementia, myoclonus and Parkinsonism, whose cerebral MRI showed mild atrophy of left temporal lobe. EEG of the new patient indicated periodic sharp wave complexes （PSWCs）. Conclusion Patients in this pedigree demonstrate the phenotype of CJD. The pedigree is autosomal dominant with incomplete penetrance.