权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Establishment of diagnosis and stem cell transplantation therapy regarding severe combined immunodeficiency

严重联合免疫缺陷诊断及干细胞移植治疗的建立

基本信息

批准号：
17591078
负责人：
AGEMATSU Kazunaga
金额：
$ 2.18万
依托单位：
SHINSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Patients with severe combined immunodeficiency (SCID) is a disorder of poor prognosis. A subgroup of SCID increased cellular radiation sensitivity (RS-SCID) have mutations of Artemis, a gene that encodes a protein essential for V(D)J recombination and DNA double-strand break repair. We have identified three Japanese boys and one girl from four unrelated families with RS-SCID caused by a genomic exon 3 deletion of the Artemis gene, resulting in loss of exon 3 and skipping of exon 4. Two patients were homozygous and two patients were heterozygous for this novel mutation. Those parents studied were heterozygous for this mutation. Although two infants underwent successful bone marrow transplantation and immune reconstitution, the long-term outcome of this procedure is uncertain, because Artemis is expressed in most tissues and lack of its function in cells other than those derived from hematopoietic stem cells may increase the risk of malignancies.A diagnosis tends to be late, and because transplantation methods are not unified, the treatment of SCID is different the hospital. We are able to establish a genetic analysis in Japan, and develop early diagnosis and hematopoietic stem cell transplantation methods of severe combined immunodeficiency by this study. In these two years, we were able to make transplantation protocol of severe combined immunodeficiency jointly. In addition, we] could do presentation of severe combined immunodeficiency and other immunodeficiency.

重症联合免疫缺陷（SCID）患者是一种预后不良的疾病。一个亚组的SCID增加细胞辐射敏感性（RS-SCID）具有Artemis突变，Artemis是一种编码V（D）J重组和DNA双链断裂修复所必需的蛋白质的基因。我们已经确定了来自四个不相关家庭的三名日本男孩和一名女孩患有由Artemis基因的基因组外显子3缺失引起的RS-SCID，导致外显子3丢失和外显子4跳跃。两名患者是纯合子，两名患者是这种新突变的杂合子。这些父母研究是杂合子的这种突变。虽然两名婴儿成功进行了骨髓移植和免疫重建，但这种手术的长期结果是不确定的，因为Artemis在大多数组织中表达，并且在造血干细胞以外的细胞中缺乏其功能可能会增加恶性肿瘤的风险。通过本研究，我们能够在日本建立遗传分析，并开发严重联合免疫缺陷症的早期诊断和造血干细胞移植方法。在这两年中，我们能够共同制定重症联合免疫缺陷的移植方案。此外，我们可以做介绍严重的联合免疫缺陷和其他免疫缺陷。