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.

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National Human Genome Research Institute
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Biesecker, Leslie G (2018) Mosaic disorders and the Taxonomy of Human Disease. Genet Med 20:800-801
Johnston, Jennifer J; van der Smagt, Jasper J; Rosenfeld, Jill A et al. (2018) Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants. Genet Med 20:1175-1185
Nathan, Neera R; Patel, Rachna; Crenshaw, Molly M et al. (2018) Pathogenetic insights from quantification of the cerebriform connective tissue nevus in Proteus syndrome. J Am Acad Dermatol 78:725-732
Biderman Waberski, Marta; Lindhurst, Marjorie; Keppler-Noreuil, Kim M et al. (2018) Urine cell-free DNA is a biomarker for nephroblastomatosis or Wilms tumor in PIK3CA-related overgrowth spectrum (PROS). Genet Med 20:1077-1081
Biesecker, Leslie G (2018) Response to Nakaguma et al. Genet Med :
Sapp, Julie C; Hu, Lian; Zhao, Jean et al. (2017) Quantifying survival in patients with Proteus syndrome. Genet Med 19:1376-1379
Yuan, Xuan; Li, Zhe; Baines, Andrea C et al. (2017) A hypomorphic PIGA gene mutation causes severe defects in neuron development and susceptibility to complement-mediated toxicity in a human iPSC model. PLoS One 12:e0174074
Nathan, Neera; Keppler-Noreuil, Kim M; Biesecker, Leslie G et al. (2017) Mosaic Disorders of the PI3K/PTEN/AKT/TSC/mTORC1 Signaling Pathway. Dermatol Clin 35:51-60
Johnston, Jennifer J; Lee, Chanjae; Wentzensen, Ingrid M et al. (2017) Compound heterozygous alterations in intraflagellar transport protein CLUAP1 in a child with a novel Joubert and oral-facial-digital overlap syndrome. Cold Spring Harb Mol Case Stud 3:
Wentzensen, Ingrid M; Johnston, Jennifer J; Patton, John H et al. (2016) Exome sequencing identifies a mutation in OFD1 in a male with Joubert syndrome, orofaciodigital spectrum anomalies and complex polydactyly. Hum Genome Var 3:15069

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