Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study
Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study
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DOI：
10.1136/bmj.38804.511644.55
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发表时间：
2006-05-20
影响因子：
--
通讯作者：
Hilton, DA
中科院分区：
文献类型：
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作者：
Ironside, JW;Bishop, MT;Hilton, DA
目的 对从疾病相关朊病毒蛋白检测呈阳性的阑尾组织样本中提取的 DNA 进行朊病毒蛋白基因 (PRNP) 密码子 129 分析。 设计 对英国变异型克雅氏病 (vCJD) 回顾性匿名非连锁患病率研究中发现的阳性病例进行重新分析。 研究样本 对 12 674 份阑尾和扁桃体样本中的 3 个阳性阑尾组织样本进行了疾病相关朊病毒蛋白检测。获得这些样本的患者在手术时年龄为 20-29 岁，手术发生于 1996 年 9 月。在英格兰和苏格兰的两个三级中心设置病理科。结果 三个样本中有两个样本有足够的 DNA 可用于分析，两个样本的 PRNP 密码子 129 处的缬氨酸都是纯合的。 结论 这是第一个表明 PRNP 密码子 129 处的缬氨酸纯合亚组易受 vCJD 感染的迹象。迄今为止，所有测试的 vCJD 临床病例均发生在蛋氨酸纯合子亚组中，并且在一名该基因位点为蛋氨酸/缬氨酸杂合子的患者中发现了一例可能的医源性 vCJD 感染。携带缬氨酸纯合密码子 129 PRNP 基因型的 vCJD 感染者可能有较长的潜伏期，在此期间，感染可能因献血或在疾病无症状阶段使用的受污染的手术器械而发生水平传播。
Objective To perform prion protein gene (PRNP) codon 129 analysis in DNA extracted from appendix tissue samples that had tested positive for disease associated prion protein.Design Reanalysis of positive cases identified in a retrospective anonymised unlinked prevalence study of variant Creutzfeldt-Jakob disease (vCJD) in the United Kingdom.Study samples Three positive appendix tissue samples out of 12 674 samples of appendix and tonsil tested for disease associated prion protein. The patients from whom these samples were obtained were aged 20-29 years at the time of surgery, which took place in 1996-9.Setting Pathology departments in two tertiary centres in England and Scotland. Results Adequate DNA was available for analysis in two of the three specimens, both of which were homozygous for valine at codon 129 in the PRNP.Conclusions This is the first indication that the valine homozygous subgroup at codon 129 in the PRNP is susceptible to vCJD infection. All tested clinical cases of vCJD have so far occurred in the methionine homozygous subgroup, and a single case of probable iatrogenic vCJD infection has been identified in one patient who was a methionine/valine heterozygote at this genetic locus. People infected with vCJD with a valine homozygous codon 129 PRNP genotype may have a prolonged incubation period, during which horizontal spread of the infection could occur either from blood donations or from contaminated surgical instruments used on these individuals during the asymptomatic phase of the illness.