The skeletal dysplasias are a heterogeneous group of disorders which result in disproportionate short stature and/or skeletal deformities. Although they have long been considered to be generalized disorders of endochondral and/or membranous ossification, the extent of their heterogeneity has only recently been recognized and little is known concerning their pathogenesis. This project is directed toward a multidisciplinary investigation of the clinical, genetic, morphologic, biochemical and molecular characteristics of the skeletal dysplasias.
The specific aims of this proposal will be: (a) expansion and further computerization of the International Skeletal Dysplasia Registry; (b) Definition of the clinical variability and genetic heterogeneity of the skeletal dysplasias; (c) definition of the natural history, growth characteristics and complications of each of these disorders and evaluation of methods for their treatment and management; (d) improvement of methods for their prenatal diagnosis; (e) clinical evaluation of medical and surgical methods of growth promotion; (f) elucidation of the histological, histochemical, immunocytochemical and ultrastructural characteristics of chondro-osseous tissue in each of these disorders; (g) elucidation of their basic biochemical defects by means of biochemical analysis of cartilage and cultured chondrocytes; (h) linkage analysis of individual syndromes with RFLP's of certain candidate genes; and (i) elucidation of their molecular defects by the analysis of collagen and proteoglycan mRNA and DNA. This program project is divided into a core facility - The International Skeletal Dysplasia Registry, plus five separate grant proposals: (1) Clinical and morphological studies; (2) Studies on differentiated chondrocytes in cultures; (3) Collagen biochemistry in the skeletal dysplasias; (4) Molecular studies in the skeletal dysplasias; (5) Analysis of proteoglycans in chondrodysplasias.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
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Special Emphasis Panel (SRC (DR))
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Javois, Lorette Claire
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Cedars-Sinai Medical Center
Los Angeles
United States
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Joeng, Kyu Sang; Lee, Yi-Chien; Lim, Joohyun et al. (2017) Osteocyte-specific WNT1 regulates osteoblast function during bone homeostasis. J Clin Invest 127:2678-2688
Madan, Simran; Liu, Wei; Lu, James T et al. (2017) A non-mosaic PORCN mutation in a male with severe congenital anomalies overlapping focal dermal hypoplasia. Mol Genet Metab Rep 12:57-61
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Hudson, David M; Joeng, Kyu Sang; Werther, Rachel et al. (2015) Post-translationally abnormal collagens of prolyl 3-hydroxylase-2 null mice offer a pathobiological mechanism for the high myopia linked to human LEPREL1 mutations. J Biol Chem 290:8613-22
Chen, Shan; Grover, Monica; Sibai, Tarek et al. (2015) Losartan increases bone mass and accelerates chondrocyte hypertrophy in developing skeleton. Mol Genet Metab 115:53-60
Weinstein, Michael M; Tompson, Stuart W; Chen, Yuqing et al. (2014) Mice expressing mutant Trpv4 recapitulate the human TRPV4 disorders. J Bone Miner Res 29:1815-1822
Joeng, Kyu Sang; Lee, Yi-Chien; Jiang, Ming-Ming et al. (2014) The swaying mouse as a model of osteogenesis imperfecta caused by WNT1 mutations. Hum Mol Genet 23:4035-42
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