Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1993 Jun;52(6):1175–1181.

Negative expansion of the myotonic dystrophy unstable sequence.

D Abeliovich 1, I Lerer 1, I Pashut-Lavon 1, E Shmueli 1, A Raas-Rothschild 1, M Frydman 1
PMCID: PMC1682287  PMID: 8503449

Abstract

We have analyzed the unstable fragment of the myotonic dystrophy (DM) gene in a pregnancy at 50% risk for DM. The affected father in this family had a 3.0-kb expansion of the DM unstable region. The fetus inherited the mutated gene, but with an expansion of 0.5 kb. This case represented a counseling problem in light of the absence of data concerning "negative expansion." Analysis of the DM gene in 17 families with 72 affected individuals revealed four more cases of negative expansions, all of them in paternal transmissions. The possible significance of this finding is discussed.

Full text

PDF
1176

Images in this article

1177Figure 2
on p.1177

Selected References

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

  1. Aslanidis C., Jansen G., Amemiya C., Shutler G., Mahadevan M., Tsilfidis C., Chen C., Alleman J., Wormskamp N. G., Vooijs M. Cloning of the essential myotonic dystrophy region and mapping of the putative defect. Nature. 1992 Feb 6;355(6360):548–551. doi: 10.1038/355548a0. [DOI] [PubMed] [Google Scholar]
  2. Brook J. D., Harley H. G., Rundle S. A., Walsh K. V., Shaw D. J. RFLP for a DNA clone which maps to 19q13.2-19qter (D19S63). Nucleic Acids Res. 1990 Aug 25;18(16):4962–4962. doi: 10.1093/nar/18.16.4962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brook J. D., McCurrach M. E., Harley H. G., Buckler A. J., Church D., Aburatani H., Hunter K., Stanton V. P., Thirion J. P., Hudson T. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992 Feb 21;68(4):799–808. doi: 10.1016/0092-8674(92)90154-5. [DOI] [PubMed] [Google Scholar]
  4. Buxton J., Shelbourne P., Davies J., Jones C., Van Tongeren T., Aslanidis C., de Jong P., Jansen G., Anvret M., Riley B. Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy. Nature. 1992 Feb 6;355(6360):547–548. doi: 10.1038/355547a0. [DOI] [PubMed] [Google Scholar]
  5. Fu Y. H., Pizzuti A., Fenwick R. G., Jr, King J., Rajnarayan S., Dunne P. W., Dubel J., Nasser G. A., Ashizawa T., de Jong P. An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science. 1992 Mar 6;255(5049):1256–1258. doi: 10.1126/science.1546326. [DOI] [PubMed] [Google Scholar]
  6. Harley H. G., Brook J. D., Rundle S. A., Crow S., Reardon W., Buckler A. J., Harper P. S., Housman D. E., Shaw D. J. Expansion of an unstable DNA region and phenotypic variation in myotonic dystrophy. Nature. 1992 Feb 6;355(6360):545–546. doi: 10.1038/355545a0. [DOI] [PubMed] [Google Scholar]
  7. Harley H. G., Rundle S. A., Reardon W., Myring J., Crow S., Brook J. D., Harper P. S., Shaw D. J. Unstable DNA sequence in myotonic dystrophy. Lancet. 1992 May 9;339(8802):1125–1128. doi: 10.1016/0140-6736(92)90729-m. [DOI] [PubMed] [Google Scholar]
  8. Harper P. S., Harley H. G., Reardon W., Shaw D. J. Anticipation in myotonic dystrophy: new light on an old problem. Am J Hum Genet. 1992 Jul;51(1):10–16. [PMC free article] [PubMed] [Google Scholar]
  9. Hunter A., Tsilfidis C., Mettler G., Jacob P., Mahadevan M., Surh L., Korneluk R. The correlation of age of onset with CTG trinucleotide repeat amplification in myotonic dystrophy. J Med Genet. 1992 Nov;29(11):774–779. doi: 10.1136/jmg.29.11.774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Koch M. C., Grimm T., Harley H. G., Harper P. S. Genetic risks for children of women with myotonic dystrophy. Am J Hum Genet. 1991 Jun;48(6):1084–1091. [PMC free article] [PubMed] [Google Scholar]
  11. Korneluk R. G., MacLeod H. L., Leblond S. C., Monteith N. L., Baralle F. E., Hunter A. G. AvaII RFLP at the human apolipoprotein CII (APO CII) gene locus. Nucleic Acids Res. 1987 Aug 25;15(16):6769–6769. doi: 10.1093/nar/15.16.6769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Korneluk R. G., MacLeod H. L., McKeithan T. W., Brooks J. D., MacKenzie A. E. A chromosome 19 clone from a translocation breakpoint shows close linkage and linkage disequilibrium with myotonic dystrophy. Genomics. 1989 Feb;4(2):146–151. doi: 10.1016/0888-7543(89)90293-0. [DOI] [PubMed] [Google Scholar]
  13. Lavedan C., Hofmann-Radvanyi H., Rabes J. P., Roume J., Junien C. Different sex-dependent constraints in CTG length variation as explanation for congenital myotonic dystrophy. Lancet. 1993 Jan 23;341(8839):237–237. doi: 10.1016/0140-6736(93)90097-z. [DOI] [PubMed] [Google Scholar]
  14. Mahadevan M., Tsilfidis C., Sabourin L., Shutler G., Amemiya C., Jansen G., Neville C., Narang M., Barceló J., O'Hoy K. Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene. Science. 1992 Mar 6;255(5049):1253–1255. doi: 10.1126/science.1546325. [DOI] [PubMed] [Google Scholar]
  15. Mulley J. C., Staples A., Donnelly A., Gedeon A. K., Hecht B. K., Nicholson G. A., Haan E. A., Sutherland G. R. Explanation for exclusive maternal origin for congenital form of myotonic dystrophy. Lancet. 1993 Jan 23;341(8839):236–237. doi: 10.1016/0140-6736(93)90096-y. [DOI] [PubMed] [Google Scholar]
  16. Perryman M. B., Hejtmancik J. F., Ashizawa T., Armstrong R., Lin S. C., Roberts R., Epstein H. F. NcoI and TaqI RFLPs for human M creatine kinase (CKM) Nucleic Acids Res. 1988 Sep 12;16(17):8744–8744. doi: 10.1093/nar/16.17.8744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shelbourne P., Winqvist R., Kunert E., Davies J., Leisti J., Thiele H., Bachmann H., Buxton J., Williamson B., Johnson K. Unstable DNA may be responsible for the incomplete penetrance of the myotonic dystrophy phenotype. Hum Mol Genet. 1992 Oct;1(7):467–473. doi: 10.1093/hmg/1.7.467. [DOI] [PubMed] [Google Scholar]
  18. Suthers G. K., Huson S. M., Davies K. E. Instability versus predictability: the molecular diagnosis of myotonic dystrophy. J Med Genet. 1992 Nov;29(11):761–765. doi: 10.1136/jmg.29.11.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tsilfidis C., MacKenzie A. E., Mettler G., Barceló J., Korneluk R. G. Correlation between CTG trinucleotide repeat length and frequency of severe congenital myotonic dystrophy. Nat Genet. 1992 Jun;1(3):192–195. doi: 10.1038/ng0692-192. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES