CRANIOFACIAL FEATURES AND TBX1 IN 22Q11 DELETION SYNDROME

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。染色体22q11缺失(del22q11.2)是一种发生在1/4000活产儿中的遗传综合征。该综合征的特征是各种身体差异，患者可能具有以下一种或多种特征：特征性面部特征、心脏缺陷、胸腺异常、甲状旁腺功能减退症、学习困难和精神障碍。大多数患有22q11缺失综合征的患者在22号染色体的一个拷贝上有一段缺失。虽然人们对了解这一复杂遗传综合征的基因-表型关系有广泛的兴趣，但很少有研究提供关于特定遗传变异的信息或客观描述这些患者的头面部表型。然而，要了解这种表型的遗传贡献，还需要进一步了解遗传差异，并对22q11缺失儿童的头面部特征进行定量描述。目前的试点研究有两个目的。主要目的是发现22q11缺失患者的遗传变异。第二个目标是继续收集数据来解决这个问题：头面部人体测量能否为临床上观察到的22q11染色体缺失患者的头面部差异提供客观和具体的描述？该项目的这一方面增加了一项研究，我们已经开始验证3DMD相机在del22q11.2儿童面部测量中的有效性。随后，我们将第一次相机验证研究称为“第一阶段”，将当前研究称为“第二阶段”的先导调查。这一试点项目的结果将提供对规划未来研究至关重要的初步数据。在这项研究的下一阶段(阶段3)，接下来将进行单独的IRB应用，我们将进行一项有充分证据(有200名参与者)的病例对照关联研究，旨在评估del22q11.2患者头面部特征和遗传差异的表型-基因关系。对这种关系的进一步了解将有助于深入了解这种复杂的遗传综合征以及典型的颅面发育背后的发育生物学。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chromosome 22q11 deletion (del22q11.2) is a genetic syndrome occurring in 1/4000 live births. The syndrome is characterized by a variety of physical differences and patients may have one or more of the following features: characteristic facial features, cardiac defects, abnormalities in the thymus gland, hypoparathyroidism, learning difficulties, and psychiatric disorders. Most patients with 22q11 deletion syndrome have a deletion of a segment on one of the copies of chromosome 22. Although there is widespread interest in understanding the genotype-phenotype relationship in this complex genetic syndrome, few studies have been designed to provide information on the specific genetic variations or to objectively delineate the craniofacial phenotype in these patients. Yet understanding the genetic contribution to this phenotype will require additional insight into the genetic differences and a quantitative description of the craniofacial features in children with the 22q11 deletion. The purpose of the current pilot study is two-fold. The primary aim is to discover genetic variants in patients with the 22q11 deletion. The second aim is to continue to gather data to address the question: can craniofacial anthropometric measurements provide an objective and specific description of craniofacial differences that are clinically observed in patients with chromosome 22q11 deletion? This aspect of the project adds to a study we have already begun to validate the 3DMD camera for facial measurements in children with del22q11.2. We subsequently refer to the first camera validation study as "Phase I" and to the current study as "Phase II" of our pilot investigations. The results of this pilot project will provide preliminary data that is critical to the planning of future studies. In the next phase of this research (phase 3), for which a separate IRB application will follow, we will perform an adequately powered (with 200 participants) case-control association study designed to assess the phenotype-genotype relationship of the craniofacial features and genetic differences in individuals with del22q11.2. Further understanding of this relationship would provide insight into the developmental biology underlying this complex genetic syndrome as well as typical craniofacial development.