Clinical and Molecular Studies of Malformations

该实验室使用转化研究方法来研究人类畸形。在临床竞技场，我们操作几个临床研究方案，以评估严重程度的范围，畸形谱，和自然史的多效性发育异常。我们使用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EEG、肺功能测试等在内的临床评价来表征功能和结构异常。在选定的情况下，我们也进行手术治疗，如果他们提供临床效益，可以提高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、变形症、Bardet-Biedl和伦茨小眼症。 我们使用现代分子生物学的工具来确定这些疾病的分子发病机制。这些包括高通量测序、定位克隆、微阵列表达和微阵列CGH分析、评估细胞生物学功能和基因产物异常的细胞和组织培养研究，以及人类遗传疾病动物模型（小鼠和斑马鱼）的创建和分析。 利用这些技术，我们已经阐明了TARP综合征（足、房间隔缺损、右上级腔静脉和腭裂）、Pallister-Hall、McKusick-Kaufman、伦茨小眼、眼面心牙综合征、丙二酸和甲基丙二酸混合血症和变形综合征的病因。

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.