Deletions of the elastin gene at 7q11.23 occur in approximately 90% of patients with Williams syndrome (original) (raw)

. 1995 May;56(5):1156–1161.

Abstract

To investigate the frequency of deletions of the elastin gene in patients with Williams syndrome (WS), we screened 44 patients by both FISH and PCR amplification of a dinucleotide repeat polymorphism. FISH was performed using cosmids containing either the 5' or the 3' end of the elastin gene. PCR analysis was performed on the patients and their parents with a (CA)n repeat polymorphism found in intron 17 of the elastin locus. Of the 44 patients screened, 91% were shown to be deleted by FISH. Using the DNA polymorphism, both maternally (39%) and paternally (61%) derived deletions were found. Four patients were not deleted for elastin but have clinical features of WS. Since deletions of elastin cannot account for several features found in WS, these patients will be valuable in further delineation of the critical region responsible for the WS phenotype. Although PCR can be useful for determining the parental origin of the deletion, our results demonstrate that FISH analysis of the elastin locus provides a more rapid and informative test to confirm a clinical diagnosis of WS. The presence of two copies of the elastin locus in a patient does not, however, rule out WS as a diagnosis.

1156

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chance P. F., Alderson M. K., Leppig K. A., Lensch M. W., Matsunami N., Smith B., Swanson P. D., Odelberg S. J., Disteche C. M., Bird T. D. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell. 1993 Jan 15;72(1):143–151. doi: 10.1016/0092-8674(93)90058-x. [DOI] [PubMed] [Google Scholar]
  2. Chiarella F., Bricarelli F. D., Lupi G., Bellotti P., Domenicucci S., Vecchio C. Familial supravalvular aortic stenosis: a genetic study. J Med Genet. 1989 Feb;26(2):86–92. doi: 10.1136/jmg.26.2.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Conway E. E., Jr, Noonan J., Marion R. W., Steeg C. N. Myocardial infarction leading to sudden death in the Williams syndrome: report of three cases. J Pediatr. 1990 Oct;117(4):593–595. doi: 10.1016/s0022-3476(05)80696-1. [DOI] [PubMed] [Google Scholar]
  4. Curran M. E., Atkinson D. L., Ewart A. K., Morris C. A., Leppert M. F., Keating M. T. The elastin gene is disrupted by a translocation associated with supravalvular aortic stenosis. Cell. 1993 Apr 9;73(1):159–168. doi: 10.1016/0092-8674(93)90168-p. [DOI] [PubMed] [Google Scholar]
  5. Ensing G. J., Schmidt M. A., Hagler D. J., Michels V. V., Carter G. A., Feldt R. H. Spectrum of findings in a family with nonsyndromic autosomal dominant supravalvular aortic stenosis: a Doppler echocardiographic study. J Am Coll Cardiol. 1989 Feb;13(2):413–419. doi: 10.1016/0735-1097(89)90520-2. [DOI] [PubMed] [Google Scholar]
  6. Ewart A. K., Jin W., Atkinson D., Morris C. A., Keating M. T. Supravalvular aortic stenosis associated with a deletion disrupting the elastin gene. J Clin Invest. 1994 Mar;93(3):1071–1077. doi: 10.1172/JCI117057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ewart A. K., Morris C. A., Atkinson D., Jin W., Sternes K., Spallone P., Stock A. D., Leppert M., Keating M. T. Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Nat Genet. 1993 Sep;5(1):11–16. doi: 10.1038/ng0993-11. [DOI] [PubMed] [Google Scholar]
  8. Ewart A. K., Morris C. A., Ensing G. J., Loker J., Moore C., Leppert M., Keating M. A human vascular disorder, supravalvular aortic stenosis, maps to chromosome 7. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3226–3230. doi: 10.1073/pnas.90.8.3226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fazio M. J., Mattei M. G., Passage E., Chu M. L., Black D., Solomon E., Davidson J. M., Uitto J. Human elastin gene: new evidence for localization to the long arm of chromosome 7. Am J Hum Genet. 1991 Apr;48(4):696–703. [PMC free article] [PubMed] [Google Scholar]
  10. Foster K., Ferrell R., King-Underwood L., Povey S., Attwood J., Rennick R., Humphries S. E., Henney A. M. Description of a dinucleotide repeat polymorphism in the human elastin gene and its use to confirm assignment of the gene to chromosome 7. Ann Hum Genet. 1993 May;57(Pt 2):87–96. doi: 10.1111/j.1469-1809.1993.tb00890.x. [DOI] [PubMed] [Google Scholar]
  11. Giddins N. G., Finley J. P., Nanton M. A., Roy D. L. The natural course of supravalvar aortic stenosis and peripheral pulmonary artery stenosis in Williams's syndrome. Br Heart J. 1989 Oct;62(4):315–319. doi: 10.1136/hrt.62.4.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Greenberg F., Ledbetter D. H. Chromosome abnormalities and Williams syndrome. Am J Med Genet. 1988 Aug;30(4):993–996. doi: 10.1002/ajmg.1320300423. [DOI] [PubMed] [Google Scholar]
  13. Indik Z., Yeh H., Ornstein-Goldstein N., Kucich U., Abrams W., Rosenbloom J. C., Rosenbloom J. Structure of the elastin gene and alternative splicing of elastin mRNA: implications for human disease. Am J Med Genet. 1989 Sep;34(1):81–90. doi: 10.1002/ajmg.1320340115. [DOI] [PubMed] [Google Scholar]
  14. Lupski J. R., Chance P. F., Garcia C. A. Inherited primary peripheral neuropathies. Molecular genetics and clinical implications of CMT1A and HNPP. JAMA. 1993 Nov 17;270(19):2326–2330. doi: 10.1001/jama.270.19.2326. [DOI] [PubMed] [Google Scholar]
  15. Lupski J. R., Wise C. A., Kuwano A., Pentao L., Parke J. T., Glaze D. G., Ledbetter D. H., Greenberg F., Patel P. I. Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A. Nat Genet. 1992 Apr;1(1):29–33. doi: 10.1038/ng0492-29. [DOI] [PubMed] [Google Scholar]
  16. Lupski J. R., de Oca-Luna R. M., Slaugenhaupt S., Pentao L., Guzzetta V., Trask B. J., Saucedo-Cardenas O., Barker D. F., Killian J. M., Garcia C. A. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell. 1991 Jul 26;66(2):219–232. doi: 10.1016/0092-8674(91)90613-4. [DOI] [PubMed] [Google Scholar]
  17. Morris C. A., Demsey S. A., Leonard C. O., Dilts C., Blackburn B. L. Natural history of Williams syndrome: physical characteristics. J Pediatr. 1988 Aug;113(2):318–326. doi: 10.1016/s0022-3476(88)80272-5. [DOI] [PubMed] [Google Scholar]
  18. Morris C. A., Thomas I. T., Greenberg F. Williams syndrome: autosomal dominant inheritance. Am J Med Genet. 1993 Sep 15;47(4):478–481. doi: 10.1002/ajmg.1320470409. [DOI] [PubMed] [Google Scholar]
  19. Olson T. M., Michels V. V., Lindor N. M., Pastores G. M., Weber J. L., Schaid D. J., Driscoll D. J., Feldt R. H., Thibodeau S. N. Autosomal dominant supravalvular aortic stenosis: localization to chromosome 7. Hum Mol Genet. 1993 Jul;2(7):869–873. doi: 10.1093/hmg/2.7.869. [DOI] [PubMed] [Google Scholar]
  20. Schinzel A. Microdeletion syndromes, balanced translocations, and gene mapping. J Med Genet. 1988 Jul;25(7):454–462. doi: 10.1136/jmg.25.7.454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schmickel R. D. Contiguous gene syndromes: a component of recognizable syndromes. J Pediatr. 1986 Aug;109(2):231–241. doi: 10.1016/s0022-3476(86)80377-8. [DOI] [PubMed] [Google Scholar]
  22. Shaffer L. G., McCaskill C., Han J. Y., Choo K. H., Cutillo D. M., Donnenfeld A. E., Weiss L., Van Dyke D. L. Molecular characterization of de novo secondary trisomy 13. Am J Hum Genet. 1994 Nov;55(5):968–974. [PMC free article] [PubMed] [Google Scholar]
  23. Shaffer L. G., Overhauser J., Jackson L. G., Ledbetter D. H. Genetic syndromes and uniparental disomy: a study of 16 cases of Brachmann-de Lange syndrome. Am J Med Genet. 1993 Sep 1;47(3):383–386. doi: 10.1002/ajmg.1320470317. [DOI] [PubMed] [Google Scholar]
  24. Uitto J., Christiano A. M., Kähäri V. M., Bashir M. M., Rosenbloom J. Molecular biology and pathology of human elastin. Biochem Soc Trans. 1991 Nov;19(4):824–829. doi: 10.1042/bst0190824. [DOI] [PubMed] [Google Scholar]