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. Genomic 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.%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.
展开▼
