Dissection of the VCFS phenotype--Palatal anomalies

VCFS表型剖析--腭部异常

• 批准号: 6414847
• 负责人: LAURA E. MITCHELL
• 金额: $ 21.13万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6414847
• 关键词: anatomy; clinical research; congenital oral /facial /cranial defect; family genetics; gene deletion mutation; gene environment interaction; gene expression; genetic mapping; genotype; human subject; molecular genetics; nucleic acid sequence; palate; questionnaires; syndrome

Velocardiofacial syndrome (VCFS) is a multiple malformation syndrome that is associated with a deletion of chromosome 22q11 in the majority of patients. The VCFS phenotype includes a broad range of features, but is most commonly characterized by the tetrad of palatal anomalies, congenital heart defects, cognitive impairment and a typical facial appearance. Individuals with VCFS usually exhibit only a subsets of these features, and the specific nature of any given feature may differ between individuals. For example, palatal anomalies are observed in approximately 50% of patients with VCFS and include overt cleft palate, submucous cleft palate, bifid uvula and velopharyngeal dysfunction. It was originally hypothesized that differences in the size of the chromosome 22q11 deletion would explain the observed variability in the VCFS phenotype. However, deletion size has not proven to be a strong phenotypic predictor, indicating that other factors-such as individual differences in genetic background and/or exposure history-must contribute to the observed variability in the VCFS phenotyped. Studies to identify specific factors that influence the VCFS phenotype will require extensive, systematically collected data from several hundred patients. We are uniquely poised to conduct studies of this nature, since the requisite data will be available through the proposed program project. The proposed project will capitalize on these data to identify the factors that influence the palatal phenotype in patients with VCFS. A comprehensive approach, integrating molecular and clinical data from patients with VCFS, will be employed to identify these factors. The proposed analyses will greatly increase our understanding of the factors that influence the palatal phenotype in patients with VCFS, and will lay the foundation for similar analyses of other phenotypic features of this syndrome.

速食综合征（VCFS）是一种多重畸形综合征，与大多数患者的染色体22q11删除有关。 VCFS表型包括广泛的特征，但最常见的特征是四齿异常，先天性心脏缺陷，认知障碍和典型的面部外观。 VCF的个体通常仅显示这些特征的子集，并且任何给定特征的特定性质在个人之间可能有所不同。例如，在大约50％的VCF患者中观察到pa骨异常，包括明显的left裂，粘膜cle裂，双叶尿布尿和咽咽功能障碍。最初假设，染色体22q11缺失大小的差异将解释VCFS表型的观察到的可变性。但是，缺失大小并未被证明是强大的表型预测因子，表明其他因素，例如遗传背景和/或暴露历史史上的个体差异，会导致VCFS被观察到的变异性。确定影响VCFS表型的特定因素的研究将需要数百名患者的大量，系统地收集的数据。我们很准备对这种性质进行研究，因为必要的数据将通过拟议的计划项目获得。拟议的项目将资本利用这些数据，以确定影响VCF患者的帕拉特表型的因素。将采用一种综合方法，该方法将VCF患者的分子和临床数据整合起来，以识别这些因素。拟议的分析将大大增加我们对影响VCF患者pa骨表型的因素的理解，并将为对该综合征的其他表型特征的类似分析奠定基础。