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目的报道常染色体显性遗传家族性朊蛋白病一家系的基因突变,并分析先证者的临床表现、神经影像和脑活体组织检查病理改变。方法收集一个家族性痴呆家系中先证者的病史、临床表现、视频脑电图、头颅 CT 和头颅 MRI 资料;先证者在知情同意下经立体定向行脑活体组织检查术,取右额叶皮质,观察 HE 染色和免疫组织化学改变;提取外周血白细胞 DNA,PCR 直接测序,分析先证者和家族部分成员的朊蛋白基因(PRNP)异常,以150名健康志愿者为对照组检验该基因异常是否为单核苷酸多态性。结果先证者的临床表现、神经影像、脑电图和脑活体组织检查病理符合朊蛋白病诊断;先证者和部分家族成员检测出 PRNP 基因 G114V 错义突变,129密码子均为甲硫氨酸/甲硫氨酸(M/M)基因型;150名健康志愿者不具有 G114V 突变。结论我们发现了一个常染色体显性遗传的家族性朊蛋白病的 PRNP 基因 G114V 突变,可能为病理突变。
Objective To report the genetic mutations in a pedigree of autosomal dominant familial prion diseases and to analyze the clinical manifestations, neuroimaging and pathological changes of probands. Methods The family history of dementia in family history of probands, clinical manifestations, video EEG, CT and cranial head MRI information; proband under informed consent by stereotactic brain biopsy, take the right frontal lobe Cortical and HE staining and immunohistochemical changes. Peripheral blood leukocyte DNA was extracted and sequenced directly by PCR. The prion protein gene (PRNP) abnormalities in probands and some familial members were analyzed. The genes were tested in 150 healthy volunteers Abnormality is a single nucleotide polymorphism. Results The clinical manifestations, neuroimaging, electroencephalogram and brain biopsy of the probands were consistent with the diagnosis of prion diseases. The probands and some of the family members detected the G114V missense mutation of PRNP gene. The 129 codons were all methionine Acid / methionine (M / M) genotype; 150 healthy volunteers did not have the G114V mutation. Conclusions We found a G114V mutation in the PRNP gene of an autosomal dominant familial prion disease that may be a pathological mutation.