The elucidation of disease gene and deletion mechanism in del 22q11.2 syndrome.

del 22q11.2综合征致病基因及缺失机制的阐明。

基本信息

批准号：
13670844
负责人：
MATSUOKA Rumiko
金额：
$ 2.24万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Conotruncal anomaly face syndrome (CAFS), DiGeorge syndrome (DGS), and velo-cardio-facial syndrome have similar but varying phenotypic spectra, I.e., cardiac defects, abnormal facies, thymic hypoplasia, cleft palate and hypocalcemia, and share deletion of 22q11.2 as a common feature. The aim of this study was to elucidate disease gene, phenotype/genotype correlation and deletion mechanism in del 22q11.2 syndrome.We investigated the genome sequence of a candidate gene for del 22q11.2 syndrome, TBX1, in patients with DGS or CAFS/VCFS without the 22q11.2 deletion. We found three de novo point mutations of TBX1 in three sporadic and familial patients. To our knowledge, this is the first report showing that mutations of TBX1 could be responsible for del 22q11.2 syndrome.To elucidate whether thrombocytopenia in del 22q11.2 syndrome patients is due to the hemizygosity of glycoprotein Ib-β and clarify the correlation between the phenotype and genotype of this gene in del 22q11.2 syndrome patie … More nts with thrombocytopenia, we also measured the protein level of glycoprotein Ib-β in del 22q11.2 syndrome patients and controls, and analyzed phenotypes other than thrombocytopenia in these patients. The results showed that thrombocytopenia in patients with del 22q11.2 syndrome, who had a larger mean platelet volume, lower agglutination to ristocetin than control patients, is due to decreased expression of glycoprotein Ib-β. Since patients with del 22q11.2 syndrome show an increased risk of developing a psychotic disorder, patients with thrombocytopenia require total management, especially for the psychotic disorders.In this study, we also showed in more detail that the chromosome breakpoints of del 22q11.2 syndrome occurred within two complex repeats, LCR22-2 and LCR22-4, that are 3 Mb apart and that the deletions arose from unequal meiotic recombination events. It is important to determine whether the chromosome breakpoints occur in clustered regions or at random sites of sequence homology, since elucidation of the mechanism in which the deletion generated is necessary. Less

Conotruncal异常面部综合征（CAFS），Digeorge综合征（DGS）和Velo-Cardio-Facial综合征具有相似但不同的表型光谱，即心脏缺陷，异常设施，胸膜下降，胸骨裂和股骨裂和下层的特征和22Q11q11Q11Q11Q11Q11。这项研究的目的是阐明DEL 22Q11.2综合征中的疾病基因，表型/基因型相关性和缺失机制。我们研究了患有DGS或CAFS/VCF的患者的DEL 22Q11.2综合征TBX1的候选基因的基因组序列。我们在三名零星和家庭患者中发现了TBX1的三个从头突变。据我们所知，这是第一份报告表明，TBX1的突变可能是DEL 22Q11.2综合征的原因。阐明DEL 22Q11.2综合征患者的血小板减少症是否是由于糖蛋白蛋白IB-β的半巧合造成的，并阐明了该基因和基因型的相关性。血小板减少症，我们还测量了DEL 22Q11.2综合征患者和对照组中糖蛋白IB-β的蛋白质水平，并分析了这些患者血小板减少症以外的其他表型。结果表明，DEL 22q11.2综合征中的血小板减少症的平均血小板体积较大，对危险患者的凝集较低，这是由于糖蛋白IB-β表达降低所致。由于患有DEL 22Q11.2综合征的患者表明患有精神病障碍的风险增加，因此血小板减少症患者需要全部治疗，尤其是对于精神病患者。在这项研究中，我们还详细介绍了DEL 22Q11.2染色体断裂点综合症发生在两个复杂重复中，LCR222-2和LCR222-22-22-22-22-4的疾病中，该综合症发生了3 MB，该疾病发生了3 MB，并且是3 MB的杂物。重组事件。重要的是要确定染色体断点是在群集区域还是在序列同源性的随机位点发生，因为阐明了产生的缺失的机制。较少的