Molecular Epidemiologic analysis of familial case including an discordant identical twin of HTLV-I associated myelopathy (HAM)

包括 HTLV-I 相关性脊髓病 (HAM) 不一致同卵双胞胎在内的家族病例的分子流行病学分析

• 批准号: 09670660
• 负责人: SHIRABE Susumu
• 金额: $ 1.86万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670660/
• 关键词: HTLV-I; HTLV-I associated myelopathy; tax; HLA anchor motif; quasispecies; synonimous mutation; non-synonimous mutation; molecular epidemiology; 非同義置

We have a case of identical twin of discordant outcome (a healthy carrier and HAM patient) of HTLV-I associated myelopathy (HAM). We investigated healthy carriers and HAM patients in this family including this twin by nucleotide sequence analysis of tax gene, viral load of HTLV-I provirus of lymphocytes, titers of serum anti-HTLV-I antibody, spontaneous proliferation of peripheral blood cells, and HLA typing.1) twenty different molecular clones were selected randomly, then tax gene amplified by nested PCR was sequenced. Eight out of 18 showed mutations were found in clones derived from LIAM patient. All clones from carrier showed mutation.2) Five mutations had non-synonymous mutations. One of change found in carrier may explain difference of immunological response to the HLA anchor motif.3) HTLV-l proviral load was significant higher in HAM patients than on carrier.4) Spontaneous proliferation was exaggerated in HAM patients.5) Nucleotide sequence of ENV also showed mutation responsible for change of HLA anchor motif iii carrier of twin.

我们有一个同卵双胞胎的不一致的结果（健康携带者和HAM患者）HTLV-I相关脊髓病（HAM）。方法：1）随机选取20个不同的分子克隆，采用巢式PCR扩增tax基因，并进行测序。18个克隆中有8个在LIAM患者的克隆中发现了突变。2）5个突变为非同义突变。HAM患者的HTLV-1前病毒载量明显高于携带者; HAM患者的自发性细胞增殖明显增强; HAM患者的ENV基因序列也发生突变，导致HLA-anchor motif发生改变。

项目成果

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