Lee H S, Sambuughin N, Cervenakova L, Chapman J, Pocchiari M, Litvak S, Qi H Y, Budka H, del Ser T, Furukawa H, Brown P, Gajdusek D C, Long J C, Korczyn A D, Goldfarb L G
Clinical Neurogenetics Unit, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
Am J Hum Genet. 1999 Apr;64(4):1063-70. doi: 10.1086/302340.
Creutzfeldt-Jakob disease (CJD) belongs to a group of prion diseases that may be infectious, sporadic, or hereditary. The 200K point mutation in the PRNP gene is the most frequent cause of hereditary CJD, accounting for >70% of families with CJD worldwide. Prevalence of the 200K variant of familial CJD is especially high in Slovakia, Chile, and Italy, and among populations of Libyan and Tunisian Jews. To study ancestral origins of the 200K mutation-associated chromosomes, we selected microsatellite markers flanking the PRNP gene on chromosome 20p12-pter and an intragenic single-nucleotide polymorphism at the PRNP codon 129. Haplotypes were constructed for 62 CJD families originating from 11 world populations. The results show that Libyan, Tunisian, Italian, Chilean, and Spanish families share a major haplotype, suggesting that the 200K mutation may have originated from a single mutational event, perhaps in Spain, and spread to all these populations with Sephardic migrants expelled from Spain in the Middle Ages. Slovakian families and a family of Polish origin show another unique haplotype. The haplotypes in families from Germany, Sicily, Austria, and Japan are different from the Mediterranean or eastern European haplotypes. On the basis of this study, we conclude that founder effect and independent mutational events are responsible for the current geographic distribution of hereditary CJD associated with the 200K mutation.
克雅氏病（CJD）属于一组朊病毒疾病，可能具有传染性、散发性或遗传性。PRNP基因中的200K点突变是遗传性CJD最常见的病因，在全球范围内，超过70%的CJD家族由该突变导致。家族性CJD的200K变异在斯洛伐克、智利和意大利，以及利比亚和突尼斯犹太人中尤为常见。为了研究与200K突变相关染色体的祖先起源，我们选择了位于20号染色体p12 - pter上PRNP基因侧翼的微卫星标记以及PRNP密码子129处的基因内单核苷酸多态性。构建了来自11个世界人群的62个CJD家族的单倍型。结果显示，利比亚、突尼斯、意大利、智利和西班牙的家族共享一种主要单倍型，这表明200K突变可能起源于单一突变事件，可能发生在西班牙，并且随着中世纪被驱逐出西班牙的西班牙裔犹太人传播到了所有这些人群中。斯洛伐克家族以及一个波兰裔家族呈现出另一种独特的单倍型。来自德国、西西里岛、奥地利和日本的家族中的单倍型与地中海或东欧的单倍型不同。基于这项研究，我们得出结论，奠基者效应和独立的突变事件导致了与200K突变相关的遗传性CJD目前的地理分布。
