Liberski P P, Barcikowska M, Cervenakova L, Bratosiewicz J, Marczewska M, Brown P, Gajdusek D C
Department of Oncology, Medical Academy Lodz, Poland.
Acta Neuropathol. 1998 Oct;96(4):425-30. doi: 10.1007/s004010050915.
We report here an unusual sporadic case of Creutzfeldt-Jakob disease (CJD) characterized by an abundance of prion protein (PrP)-immunopositive kuru and multicentric but not florid plaques. Molecular genetic analysis of the PRNP open reading frame region spanning codons 8-221 was performed. Neither deletion nor insertion mutations were detected in the repeat area of the PRNP. No pathogenic mutation was found in the sequenced region between codon 108-221. Restriction analysis of the amplified fragment using restriction endonucleases DdeI, PvuII and AluI did not show any of the previously described pathogenic mutations at codon 102, 105, and 117 associated with Gerstmann-Sträussler-Scheinker (GSS). The patient was heterozygous for the methionine/valine coding triplet at polymorphic codon 129 of the PRNP gene by sequence, restriction endonuclease analysis and hybridization with allele-specific nucleotides. Furthermore, hybridization with 32P-labeled allele-specific oligonucleotides confirmed the absence of pathogenic mutations at codons 102, 200 and 178. Such a case may present a missing "link" between sporadic CJD and familial GSS.
我们在此报告一例罕见的散发性克雅氏病（CJD）病例，其特征为大量朊蛋白（PrP）免疫阳性的库鲁斑和多中心但非典型性斑块。对PRNP开放阅读框区域（跨越密码子8 - 221）进行了分子遗传学分析。在PRNP的重复区域未检测到缺失或插入突变。在密码子108 - 221之间的测序区域未发现致病突变。使用限制性内切酶DdeI、PvuII和AluI对扩增片段进行限制性分析，未显示与格斯特曼 - 施特劳斯勒 - 谢克尔病（GSS）相关的密码子102、105和117处的任何先前描述的致病突变。通过测序、限制性内切酶分析以及与等位基因特异性核苷酸杂交，该患者在PRNP基因的多态性密码子129处为甲硫氨酸/缬氨酸编码三联体的杂合子。此外，与32P标记的等位基因特异性寡核苷酸杂交证实了密码子102、200和178处不存在致病突变。这样的病例可能代表散发性CJD和家族性GSS之间缺失的“环节”。
