Clinical and Molecular Studies of Malformations

畸形的临床和分子研究

• 批准号: 8350002
• 负责人: Leslie Biesecker
• 金额: $ 301.36万
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8350002
• 关键词: Animal Model; Atrial Heart Septal Defects; Cells; Cleft Palate; Clinical; Clinical Research Protocols; Congenital Abnormality; Development; Diagnostic radiologic examination; Disease; Electroencephalography; Etiology; Heart Diseases; Hereditary Disease; Human; Human Genetics; Image; Laboratories; Microphthalmos; Molecular; Molecular Biology; Molecular Genetics; Mus; Natural History; Operative Surgical Procedures; Other Genetics; Pathogenesis; Physical Examination; Polydactyly; Proteins; Proteus; Proteus Syndrome; Pulmonary function tests; Recording of previous events; Severities; Superior vena cava structure; Syndrome; Techniques; Translational Research; Ultrasonography; Zebrafish; malformation; methylmalonic aciduria; positional cloning; research clinical testing; tissue/cell culture; tomography; tool

The laboratory uses a translational research approach to study human malformations. In the clinical arena, we operate several clinical research protocols to assess the range of severity, spectrum of malformations, and natural history of pleiotropic developmental anomalies. We use clinical evaluations that include history and physical examination, imaging studies including radiography, ultrasound, and tomography, as well as EEG, pulmonary function testing, etc. to characterize functional and structural anomalies. In selected cases we also perform surgical treatments if they offer clinical benefit and can advance our understanding of the disease under study. Some of the disorders that we are currently studying include non-syndromic polydactyly, Proteus, Bardet-Biedl, and Lenz microphthalmia. We use the tools of modern molecular biology to determine the molecular pathogenesis of these disorders. These include high throughput sequencing, positional cloning, microarray expression and microarray CGH analysis, cell and tissue culture studies to assess cell biologic functions and abnormalities of gene products, and the creation and analysis of animal models of human genetic disease (mouse and zebrafish). Using these techniques we have elucidated the etiology of TARP syndrome (Talipes, Atrial septal defect, Right superior vena cava, and cleft Palate), Pallister-Hall, McKusick-Kaufman, Lenz microphthalmia, Oculofaciocardiodental syndromes, combined malonic and methylmalonic acidemia, and Proteus syndrome.

该实验室采用转化研究方法来研究人体畸形。在临床领域，我们采用了几种临床研究方案来评估严重程度、畸形谱和多效性发育异常的自然史。我们使用临床评估，包括病史和体格检查，影像学研究，包括x线摄影，超声和断层扫描，以及脑电图，肺功能测试等来表征功能和结构异常。在选定的病例中，我们也会进行手术治疗，如果它们能提供临床益处，并能促进我们对所研究疾病的理解。我们目前正在研究的一些疾病包括非综合征性多指畸形、Proteus、Bardet-Biedl和Lenz小眼症。