摘要
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 a large family with an autosomal dominant dementia associated with mutation in the prion protein gene （PRNP） and the detailed clinical, neuroimaging and pathological manifestations. Methods Two patients from a large family of dementia were admitted to our ward and the data of their medical history, physical examination, video electroenceplialogram, neuroimaging were colleted. A sterotactic biopsy of the right frontal lobe of the proband was done. After the informed consent from the family members obtained, the genomic DNA was extracted from peripheral blood leucocytes of 5 persons followed by in vitro amplification using polymerase chain reaction （PCR）. The PCR products were directly sequenced by Sanger method. PRNP gene sequence was also examined in 150 normal Chinese to exclude single nucleotide polymorphism. Results A missense mutation of PRNP gene in 5 family members was detected, resulting in Gll4V mutation in the prion protein, with M/M genotype of cedon 129. This mutation was not detected in 150 normal Chinese. The proband was diagnosed as inherited prion disease by her clinical features, including neuropsychiatric disturbances and progressive dementia, and manifestations of neuroimaging, EEG, neuropathology and PRNP gene mutation. Conclusion The first autosomal dominant pedigree of family prion disease is found in China with G114V mutation in PRNP gene which may lead to the prion disease directly.
出处
《中华神经科杂志》
CAS
CSCD
北大核心
2007年第11期732-735,共4页
Chinese Journal of Neurology
关键词
克-亚综合征
朊病毒
突变
系谱
Creutzfeldt-Jakob syndrome
Prions
Mutation
Pedigree
