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Science 26 May 1989:
Vol. 244. no. 4907, pp. 978 - 980
DOI: 10.1126/science.2543071
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Articles

Science, Vol 244, Issue 4907, 978-980
Copyright © 1989 by American Association for the Advancement of Science

articles

Identification of the molecular defect in a family with spondyloepiphyseal dysplasia

B Lee, H Vissing, F Ramirez, D Rogers, and D Rimoin

Department of Microbiology and Immunology, State University of New York Health Science Center, Brooklyn 11203.

Spondyloepiphyseal dysplasias (SED) are a heterogeneous group of inherited disorders characterized by disproportionate short stature and pleiotropic involvement of the skeletal and ocular systems. Evidence has suggested that SED may result from structural defects in type II collagen. To confirm the validity of this hypothesis, the structure of the "candidate" type II collagen gene (COL2A1) has been directly examined in a relatively large SED family. Coarse scanning of the gene by Southern blot hybridization identified an abnormal restriction pattern in one of the affected members of the kindred. Analysis of selected genomic fragments, amplified by the polymerase chain reaction, precisely localized the molecular defect and demonstrated that all affected family members carried the same heterozygous single-exon deletion. As a consequence of the mutation, nearly 90 percent of the assembled type II collagen homotrimers are expected to contain one or more procollagen subunits harboring an interstitial deletion of 36 amino acids in the triple helical domain.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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The diagnosis of art: Achilles Emperaire and spondyloepiphyseal dysplasia congenita.
M. Ramachandran and J. K Aronson (2007)
J R Soc Med 100, 384-385
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Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation.
O. Barbieri, S. Astigiano, M. Morini, S. Tavella, A. Schito, A. Corsi, D. D. Martino, P. Bianco, R. Cancedda, and S. Garofalo (2003)
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A glycine to aspartic acid substitution of COL2A1 in a family with the Strudwick variant of spondyloepimetaphyseal dysplasia.
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Positional cloning of the gene LIMBIN responsible for bovine chondrodysplastic dwarfism.
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Report of five novel and one recurrent COL2A1 mutations with analysis of genotype-phenotype correlation in patients with a lethal type II collagen disorder.
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Skeletal dysplasias.
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Structurally Abnormal Type II Collagen in a Severe Form of Kniest Dysplasia Caused by an Exon 24 Skipping Mutation.
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Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan.
H. Watanabe, K. Nakata, K. Kimata, I. Nakanishi, and Y. Yamada (1997)
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Use of a New Rat Chondrosarcoma Cell line to Delineate a 119-Base Pair Chondrocyte-specific Enhancer Element and to Define Active Promoter Segments in the Mouse Pro-alpha1(II) Collagen Gene.
K. Mukhopadhyay, Vér. Lefebvre, G. Zhou, S. Garofalo, J. H. Kimura, and B. de Crombrugghe (1995)
J. Biol. Chem. 270, 27711-27719
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A COL2A1 Mutation in Achondrogenesis Type II Results in the Replacement of Type II Collagen by Type I and III Collagens in Cartilage.
D. Chan, W. G. Cole, C. W. Chow, S. Mundlos, and J. F. Bateman (1995)
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A 182 bp fragment of the mouse pro alpha 1(II) collagen gene is sufficient to direct chondrocyte expression in transgenic mice.
G Zhou, S Garofalo, K Mukhopadhyay, V Lefebvre, C. Smith, H Eberspaecher, and B de Crombrugghe (1995)
J. Cell Sci. 108, 3677-3684
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