Clinical and Molecular Studies of Malformations

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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.