MOLECULAR GENETICS OF FAMILIAL TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES

遗传性家系的分子遗传学研究 海绵状脑病(TSE)引起关注的原因是：(1) 阐明PRNP基因点突变在人类基因组中的分布 世界；(2)发现与疾病有关的新突变；以及 (3)研究突变与某些疾病表型的关系。 两个新家庭，其中一个是爱尔兰血统，具有致命的表型 家族性失眠(FFI)在澳大利亚被发现。一个FFI家庭 是在爱尔兰发现的。分子遗传学分析揭示了 Met at基因的致病点突变D178N 在这些家系中的第129位确认了诊断。一个新的 携带致病突变的克雅病家系 密码子200 Glu to Lys在美国被检测到。显然是在七年内 散发性病例，两个点突变D178N，E299K突变，120个碱基 发现插入突变和3个24碱基缺失突变。这 事实表明，评估疑似TSE病例对 PRNP基因突变的存在。检测到插入突变 一名来自南非的患者表明这种病毒的传播范围更广 突变。

The molecular genetic studies of families afflicted with transmissible spongiform encephalopathies (TSEs) is of interest in order to: (1) clarify the distribution of point mutations in the PRNP gene around the world; (2) discover the new mutations associated with the disease; and (3) study association of the mutations with certain disease phenotype. Two new families, one of them of Irish origin, having phenotype of fatal familial insomnia (FFI) were discovered in Australia. One FFI family was found in Ireland. Molecular genetic analysis revealed presence of the pathogenic point mutation D178N on the allele coding for Met at position 129 in these families confirming the diagnosis. One new Creutzfeldt-Jakob disease family carrying the pathogenic mutation at codon 200 Glu to Lys was detected in America. In seven apparently sporadic cases, two point mutations D178N, E299K mutations, 120 bp insertion mutation and three 24 bp deletion mutations were found. This fact points to the importance of evaluation of suspected TSE cases for the presence of PRNP gene mutations. Insertion mutation was detected in a patient from South Africa indicating the wider spread of such mutations.