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Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome


Williams syndrome (WS) is a developmental disorder affecting connective tissue and the central nervous system. A common feature of WS, supravalvular aortic stenosis, is also a distinct autosomal dominant disorder caused by mutations in the elastin gene. In this study, we identified hemizygosity at the elastin locus using genetic analyses in four familial and five sporadic cases of WS. Fluorescent in situ hybridization and quantitative Southern analyses confirmed these findings, demonstrating inherited and de novo deletions of the elastin gene. These data indicate that deletions involving one elastin allele cause WS and implicate elastin hemizygosity in the pathogenesis of the disease.

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  1. 1

    Beuren, A.J. Supravalvular aortic stenosis: a complex syndrome with and without mental retardation. Birth Defects 8, 45–46 (1972).

    Google Scholar 

  2. 2

    Morris, C.A., Demsey, S.A., Leonard, C.O., Dilts, C. & Blackburn, B.L. Natural history of Williams syndrome. J. Pediatr. 113, 318–326 (1988).

    CAS  Article  Google Scholar 

  3. 3

    Bellugi, U., Bihrle, A., Jernigan, T., Trauner, D. & Doherty, S., rophysical, neurological, and neuroanatomical profile of Williams syndrome. Am. J. med. Genet. 6, 115–125 (1990).

    CAS  Google Scholar 

  4. 4

    Dilts, C., Morris, C. & Leonard, C. Hypothesis for development of a behavioral phenotype in Williams syndrome. Am. J. med. Genet. 6, 126–131 (1990).

    CAS  Google Scholar 

  5. 5

    Chevers, N. Observations on the diseases of the orifice and valves of the aorta. Guys Hosp. Rep. 7, 387–421 (1842).

    Google Scholar 

  6. 6

    Eisenberg, R., Young, D., Jacobson, B. & Voito, A. Familial supravalvular aortic stenosis. Am J. Dis. Child. 108, 341–347 (1964).

    CAS  PubMed  Google Scholar 

  7. 7

    Ewart, A.K. et al. A human vascular disorder, supravalvuar aortic stenosis, maps to chromosome 7. Proc. natn. Acad. Sci. U.S.A. 90, 3226–3230 (1993).

    CAS  Article  Google Scholar 

  8. 8

    Curran, M.E. et al. The eiastin gene is disrupted by a translocation associated with supravalvular aortic stenosis. Cell 73, 159–168 (1993).

    CAS  Article  Google Scholar 

  9. 9

    Morris, C., Thomas, I.T. & Greenberg, F. Williams syndrome: autosomal dominant inheritance. Am. J. med. Genet. (in the press).

  10. 10

    Tromp, G. et al. A to G polymorphism in ELN gene. Nucl. Acids Res. 19, 4314 (1991).

    CAS  Article  Google Scholar 

  11. 11

    Perou, M. Congenital supravalvular aortic stenosis. Arch. Pathol. 71, 113–126 (1961).

    Google Scholar 

  12. 12

    O'Connor, W. et al. Supravalvular aortic stenosis: clinical and pathologic observations in six patients. Arch. Pathol. Lab. Med. 109, 179–185 (1985).

    CAS  PubMed  Google Scholar 

  13. 13

    Morris, C.A., Loker, J., Ensing, G. & Stock, A.D. Supravalvular aortic stenosis cosegregates with a familial 6;7 translocation which disrupts the elastin gene. Am. J. med. Genet. 46, 737–744 (1993).

    CAS  Article  Google Scholar 

  14. 14

    Wahl, G.M. et al. Cosmid vectors for rapid genomic walking, restriction mapping, and gene transfer. Proc. natn. Acad. Sci. U.S.A. 84, 2160–2164 (1987).

    CAS  Article  Google Scholar 

  15. 15

    Benton, W.D. & Davis, R.W. Screening I-gt recombinant clones by hybridization to single plaques in situ. Science 196, 180–182 (1977).

    CAS  Article  Google Scholar 

  16. 16

    Southern, E.M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. molec. Biol. 98, 503–517 (1975).

    CAS  Article  Google Scholar 

  17. 17

    Curran, M.E., Landes, G.M. & Keating, M.T. Molecular cloning, characterization and genomic organization of a human cardiac potassium channel gene. Genomics 12, 729–737 (1992).

    CAS  Article  Google Scholar 

  18. 18

    Kunkel, L.M. et al. Analysis of human Y-chromosome-specific reiterated DNA in chromosome variants. Proc. natn. Acad. Sci. U.S.A 74, 1245–1249 (1977).

    CAS  Article  Google Scholar 

  19. 19

    Goodman, B.K., Xu, W., Nottoli, V., Rundall-Jackson, T. & Stock, A.D. A simple technique for bone marrow preparations with modified hypotonic treatment. Karyogram 11, 95–96 (1985).

    Google Scholar 

  20. 20

    Klever, M., Grond-Ginsbach, C., Scherthan, H. & Schroeder-Kurth, T.M., Chromosomal in situ hybridization after giemsa banding. Hum. Genet. 86, 484–486 (1991).

    CAS  Article  Google Scholar 

  21. 21

    Pinkel, D. et al. Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc. natn. Acad. Sci. U.S.A. 85, 9138–9142 (1988).

    CAS  Article  Google Scholar 

  22. 22

    Tkachuk, D. et al. Detection of bcr-abl fusion in chronic myelogeneous leukemia by in situ hybridization. Science 250, 559–562 (1990).

    CAS  Article  Google Scholar 

  23. 23

    Fazio, M.J. et al. Human elastin gene: new evidence for localization of elastin to the long arm of chromosome 7. Am. J. hum. Genet. 48, 696–703 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24

    O'Connell, P. et al. Twenty loci form a continuous linkage map of marker for human chromosome 2. Genomics 5, 738–745 (1989).

    CAS  Article  Google Scholar 

  25. 25

    Vogelstein, B. et al. Allelotype of colorectal carcinomas. Science 244, 207–211 (1989).

    CAS  Article  Google Scholar 

  26. 26

    Nakamura, Y. et al. Variable number of tandem repeat markers for human gene mapping. Science 235, 1616–1622 (1987).

    CAS  Article  Google Scholar 

  27. 27

    Nakamura, Y. et al. A mapped set of DNA markers for human chromosome 17. Genomics 2, 302–309 (1988).

    CAS  Article  Google Scholar 

  28. 28

    Preus, M., Williams syndrome: Objective definition and diagnosis. Clin. Genet. 24, 433–438 (1984).

    Google Scholar 

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Ewart, A., Morris, C., Atkinson, D. et al. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat Genet 5, 11–16 (1993).

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