Skip to main content
Log in

Presence of telomeric and subtelomeric sequences at the fusion points of ring chromosomes indicates that the ring syndrome is caused by ring instability

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

In situ hybridization of a telomeric (TTA-GGG) n sequence to metaphases from three cases of ring chromosome, involving respectively chromosomes 4, 16, and 20, showed the presence of the cognate sequences in all three rings. To investigate whether these ring chromosomes originated by telomere-telomere fusion, we determined, by in situ hybridization, whether telomere-associated sequences and/or specific distal sequences were still present in the ring chromosomes. The finding that these sequences were preserved in all the ring chromosomes strongly indicates that they originated by telomere-telomere fusion. All three subjects carrying the ring chromosomes are affected by the so-called ring syndrome, with failure to thrive, minor dysmorphic signs and no major anomalies. The r(4) patient has the ring in mosaic form with a normal cell line and has normal intelligence. The r(16) and the r(20) patients have moderate mental retardation and suffer from seizures. We conclude that the ring syndrome, even in its more severe manifestation, is caused by ring chromosome instability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Altherr MR, Bengtsson U, Elder FFB, Ledbetter DH, Wasmuth JJ, McDonald ME, Gusella JF, Greenberg F (1991) Molecular confirmation of Wolf-Hirschhorn syndrome with a subtle translocation of chromosome 4. Am J Hum Genet 49:1235–1242

    Google Scholar 

  • Brown WRA, MacKinnon PJ, Villasanté A, Spurr N, Buckle VJ, Dobson MJ (1990) Structure and polymorphism of human telomere-associate DNA. Cell 63:119–132

    Google Scholar 

  • Buetow KH, Shiang R, Yang P, Nakamura Y, Lathrop GM, White R, Wasmuth JJ, Wood S, Berdahl LD, Leysens NJ (1991) A detailed multipoint map of human chromosome 4 provides evidence for linkage heterogeneity and position-specific recombination rates. Am J Hum Genet 48:911–925

    Google Scholar 

  • Cote GB, Katsantoni A, Deligeorgis D (1981) The cytogenetic and clinical implications of a ring chromosome 2. Ann Génét (Paris) 24:231–235

    Google Scholar 

  • Hastie ND, Allshire RC (1989) Human telomeres: fusion and interstitial sites. Trends Genet 5:326–331

    Article  CAS  PubMed  Google Scholar 

  • Ijdo JW, Baldini A, Ward DC, Reeders ST, Wells RA (1991) Origin of human chromosome 2: an ancestral telomere-telomere fusion. Proc Natl Acad Sci USA 88:9051–9055

    CAS  PubMed  Google Scholar 

  • Kosztolanyi G (1987) Does “ring syndrome” exist? An analysis of 207 case reports on patients with a ring autosome. Hum Genet 75:174–179

    Google Scholar 

  • MacDermott FD, Jack E, Cooke A, Turleau C, Lindenbaum RH, Pearson J, Patel C, Barnes PM, Portch J, Crawfurd M d'A (1990) Investigation of three patients with “ring syndrome”, including familial transmission of ring 5, and extimation of reproductive risks. Hum Genet 85:516–520

    Google Scholar 

  • Moyzis RK, Buckingam JM, Cram LS, Dani M, Deaven LL, Jones MD, Meyne J, Ratliff RL, Wu JR (1988) A highly conserved repetitive DNA sequence, (TTAGGG) n , present at the telomeres of human chromosomes. Proc Natl Acad Sci USA 85:6622–6626

    CAS  PubMed  Google Scholar 

  • Ohashi H, Tsukahara M, Murano I, Naritomi K, Nishioka K, Miyake S, Kajii T (1992) Pigmentary dysplasias and chromosomal mosaicism: report of 9 cases. Am J Med Genet 43:716–721

    Google Scholar 

  • Park VM, Gustashaw KM, Wathen TM (1992) The presence of interstitial telomeric sequences in constitutional chromosome abnormalities. Am J Hum Genet 50:914–923

    Google Scholar 

  • Saltman D, Ross FM, Fantes JA, Allshire R, Turner GE, Evans HJ (1989) Telomeric associations in a lymphoblastoid cell line from a patient with B-cell follicular lymphoma. Cytogenet Cell genet 50:230–233

    Google Scholar 

  • Sanna R, Fogu G, Tondi M, Serra G, Pasquali F, Danesino C (1991) In: Neri G, Di Natale P, Forabosco A, Savi M (eds) Atti del 6°Congresso Nazionale FISME, Monduzzi Bologna, pp 369–372

    Google Scholar 

  • Schinzel A (1984) Catalogue of unbalanced chromosome aberrations in man. Gruyter, Berlin New York, pp 161–164

    Google Scholar 

  • Thomas IT, Frias JL, Cantu ES, Lafer CZ, Flannery DB, Graham JG (1989) Association of pigmentary anomalies with chromosomal and genetic mosaicism and chimerism. Am J Hum Genet 15:193–205

    Google Scholar 

  • Vianello MG, Cottafava F, Bartoli D, Franzone G, Casazzava R, Gastaldi R (1990) Ring chromosome 16: a new case. Ann Genet (Paris) 33:36–39

    Google Scholar 

  • Wilkie AOM, Higgs DR, Rack KA, Buckle VJ, Spurr NK, Fischel-Ghodsian N, Ceccherini I, Brown RA, Harris PC (1991) Stable length polymorphism of up to 260 kb at the tip of the short arm of human chromosoe 16. Cell 64:595–606

    Google Scholar 

  • Youngman S, Bates GP, Williams S, McClatchey AI, Baxendale S, Sedlacek Z, Altherr M, Wasmuth JJ, MacDonald ME, Gusella JF, Sheer D, Lehrach H (1992) The telomeric 60 kb of hromosome arm 4p is homologous to telomeric regions on 13p, 15p, 21p, and 22p. Genomics 14:350–356

    Google Scholar 

  • Zuffardi O, Danesino C, Poloni L, Pavesi F, Bianchi C, Gargantini L (1980) Ring chromosome 12 and latent centromeres. Cytogenet Cell Genet 28:151–157

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pezzolo, A., Gimelli, G., Cohen, A. et al. Presence of telomeric and subtelomeric sequences at the fusion points of ring chromosomes indicates that the ring syndrome is caused by ring instability. Hum Genet 92, 23–27 (1993). https://doi.org/10.1007/BF00216140

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00216140

Keywords

Navigation