GENETIC ANALYSIS OF THE PRNP GENE IN KURU

PRNP多态(蛋氨酸/缬氨酸)密码子 129个基因型影响遗传性猪的表型特征 海绵状脑病(TSE)。所有新变种的检测病例 克雅氏病(NvCJD)是纯合子的 蛋氨酸，推测是否不同的基因类型，如果他们 可能具有不同的表型和含义 新城疫未来的“流行曲线”。小麦品种的表型-基因型研究 库鲁，唯一的另一种口头传播的TSE，可能对 预测这些问题的答案。因此我们提取了 对92例库鲁病患者血凝块或血清中的DNA进行分析 129位密码子PRNP基因分型与发病年龄的关系 和病程，在9个病例中，详细的临床和 神经病理学数据。第129密码子的纯合性(特别是对于 (甲硫氨酸)与较早的发病年龄和 更短的病程，这是杂合子，但其他 所有基因型的临床特征都是相似的。在九个月中 神经病理检查的病例，组织学上的存在 可识别的斑块仅限于携带至少一个 蛋氨酸等位基因(3个纯合子和1个杂合子)。如果 NvCJD的表现就像库鲁，未来的病例(潜伏期更长 周期)可能发生在具有杂合子的老年个体中 密码子129，标志着nvCJD的成熟进化 “流行病”。这些病例的临床表型应该是相似的。 与纯合子病例相同，但可能较少(或至少很容易 已鉴定)淀粉样斑块形成。

The PRNP polymorphic (methionine/valine) codon 129 genotype influences the phenotypic features of transmissible spongiform encephalopathy (TSE). All tested cases of new variant Creutzfeldt-Jakob disease (nvCJD) have been homozygous for methionine, and it is conjectural whether different genotypes, if they appear, might have distinctive phenotypes and implications for the future "epidemic curve" of nvCJD. Genotype-phenotype studies of kuru, the only other orally transmitted TSE, might be instructive in predicting the answers to these questions. We therefore extracted DNA in blood clots or sera from 92 kuru patients, and analyzed their codon 129 PRNP genotypes with respect to the age at onset and duration of illness, and in nine cases, to detailed clinical and neuropathology data. Homozygosity at codon 129 (particularly for methionine) was associated with an earlier age at onset and a shorter duration of illness thatn was heterozygosity, but other clinical characteristics were similar for all genotypes. In the nine neuropathologically examined cases, the presence of histologically recognizable plaques was limited to cases carrying at least one methionine allele (three homozygotes and one heterozygote). If nvCJD behaves like kuru, future cases (with longer incubation periods) may being to occur in older individuals with heterozygous codon 129 genotypes, and signal a maturing evolution of the nvCJD "epidemic". The clinical phenotype of such cases should be similar to that of homozygous cases, but may have less (or at least readily identified) amyloid plaque formation.