Skip to main content
PMC home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1991 Nov;49(5):995–1013.

De novo balanced chromosome rearrangements and extra marker chromosomes identified at prenatal diagnosis: clinical significance and distribution of breakpoints.

D Warburton 1
PMCID: PMC1683246  PMID: 1928105

Abstract

A questionnaire sent to major cytogenetics laboratories in the United States and Canada over a 10-year period collected data on the frequency and outcome of cases with either apparently balanced de novo rearrangements or de novo supernumerary marker chromosomes detected at amniocentesis. Of 377,357 reported amniocenteses, approximately 1/2,000 had a de novo reciprocal translocation, 1/9,000 a Robertsonian translocation, 1/10,000 a de novo inversion, and 1/2,500 an extra structurally abnormal chromosome of unidentifiable origin. The risk of a serious congenital anomaly was estimated to be 6.1% (n = 163) for de novo reciprocal translocations, 3.7% (n = 51) for Robertsonian translocations, and 9.4% (n = 32) for inversions. The combined risk for reciprocal translocations and inversions was 6.7% (95% confidence limits 3.1%-10.3%). The risk of abnormality for extra nonsatellited marker chromosomes was 14.7% (n = 68), and that for satellited marker chromosomes was 10.9% (n = 55). In non-Robertsonian rearrangements, distribution of breakpoints among chromosomes was not as would be expected strictly on the basis of length. Most breaks were stated to occur within G-negative bands, but there was little evidence of particular hot spots among these bands. Nevertheless, there did appear to be a correlation between those bands in which breakage was observed most often and those bands where common or rare fragile sites have been described.

Full text

PDF
995

Selected References

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

  1. Aurias A., Prieur M., Dutrillaux B., Lejeune J. Systematic analysis of 95 reciprocal translocations of autosomes. Hum Genet. 1978 Dec 29;45(3):259–282. doi: 10.1007/BF00278725. [DOI] [PubMed] [Google Scholar]
  2. Benn P. A., Hsu L. Y. Incidence and significance of supernumerary marker chromosomes in prenatal diagnosis. Am J Hum Genet. 1984 Sep;36(5):1092–1102. [PMC free article] [PubMed] [Google Scholar]
  3. Bodrug S. E., Roberson J. R., Weiss L., Ray P. N., Worton R. G., Van Dyke D. L. Prenatal identification of a girl with a t(X;4)(p21;q35) translocation: molecular characterisation, paternal origin, and association with muscular dystrophy. J Med Genet. 1990 Jul;27(7):426–432. doi: 10.1136/jmg.27.7.426. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bogart M. H., Bradshaw C. L., Jones O. W., Schanberger J. E. Prenatal diagnosis and follow up of a child with a complex chromosome rearrangement. J Med Genet. 1986 Apr;23(2):180–183. doi: 10.1136/jmg.23.2.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boué A., Gallano P. A collaborative study of the segregation of inherited chromosome structural rearrangements in 1356 prenatal diagnoses. Prenat Diagn. 1984 Spring;4(Spec No):45–67. doi: 10.1002/pd.1970040705. [DOI] [PubMed] [Google Scholar]
  6. Breg W. R., Miller D. A., Allderdice P. W., Miller O. J. Identification of translocation chromosomes by quinacrine fluorescence. Am J Dis Child. 1972 Jun;123(6):561–564. doi: 10.1001/archpedi.1972.02110120085007. [DOI] [PubMed] [Google Scholar]
  7. Buckton K. E., Spowart G., Newton M. S., Evans H. J. Forty four probands with an additional "marker" chromosome. Hum Genet. 1985;69(4):353–370. doi: 10.1007/BF00291656. [DOI] [PubMed] [Google Scholar]
  8. Budarf M., Sellinger B., Griffin C., Emanuel B. S. Comparative mapping of the constitutional and tumor-associated 11;22 translocations. Am J Hum Genet. 1989 Jul;45(1):128–139. [PMC free article] [PubMed] [Google Scholar]
  9. Callen D. F., Freemantle C. J., Ringenbergs M. L., Baker E., Eyre H. J., Romain D., Haan E. A. The isochromosome 18p syndrome: confirmation of cytogenetic diagnosis in nine cases by in situ hybridization. Am J Hum Genet. 1990 Sep;47(3):493–498. [PMC free article] [PubMed] [Google Scholar]
  10. Cheung S. W., Crane J. P., Beaver H. Correlation between phenotypic expression of de novo marker chromosomes and genomic organization using replicational banding. Prenat Diagn. 1990 Nov;10(11):717–724. doi: 10.1002/pd.1970101105. [DOI] [PubMed] [Google Scholar]
  11. Daniel A., Boué A., Gallano P. Prospective risk in reciprocal translocation heterozygotes at amniocentesis as determined by potential chromosome imbalance sizes. Data of the European Collaborative Prenatal Diagnosis Centres. Prenat Diagn. 1986 Sep-Oct;6(5):315–350. doi: 10.1002/pd.1970060502. [DOI] [PubMed] [Google Scholar]
  12. Fraccaro M., Lindsten J., Ford C. E., Iselius L. The 11q;22q translocation: a European collaborative analysis of 43 cases. Hum Genet. 1980;56(1):21–51. doi: 10.1007/BF00281567. [DOI] [PubMed] [Google Scholar]
  13. Fryns J. P., Kleczkowska A., Kubień E., Van den Berghe H. Excess of mental retardation and/or congenital malformation in reciprocal translocations in man. Hum Genet. 1986 Jan;72(1):1–8. doi: 10.1007/BF00278808. [DOI] [PubMed] [Google Scholar]
  14. Funderburk S. J., Spence M. A., Sparkes R. S. Mental retardation associated with "balanced" chromosome rearrangements. Am J Hum Genet. 1977 Mar;29(2):136–141. [PMC free article] [PubMed] [Google Scholar]
  15. Grass F. S., Parke J. C., Jr, Hisley J. C. Antenatal diagnosis of a de novo paracentric inversion of chromosome 11. Prenat Diagn. 1987;7(1):1–5. doi: 10.1002/pd.1970070102. [DOI] [PubMed] [Google Scholar]
  16. Hecht F., Hecht B. K. Fragile sites and chromosome breakpoints in constitutional rearrangements I. Amniocentesis. Clin Genet. 1984 Sep;26(3):169–173. doi: 10.1111/j.1399-0004.1984.tb04363.x. [DOI] [PubMed] [Google Scholar]
  17. Hook E. B., Cross P. K. Extra structurally abnormal chromosomes (ESAC) detected at amniocentesis: frequency in approximately 75,000 prenatal cytogenetic diagnoses and associations with maternal and paternal age. Am J Hum Genet. 1987 Feb;40(2):83–101. [PMC free article] [PubMed] [Google Scholar]
  18. Hook E. B., Healy N. P., Willey A. M. How much difference does chromosome banding make? Adjustments in prevalence and mutation rates of human structural cytogenetic abnormalities. Ann Hum Genet. 1989 Jul;53(Pt 3):237–242. doi: 10.1111/j.1469-1809.1989.tb01790.x. [DOI] [PubMed] [Google Scholar]
  19. Jacobs P. A., Buckton K. E., Cunningham C., Newton M. An analysis of the break points of structural rearrangements in man. J Med Genet. 1974 Mar;11(1):50–64. doi: 10.1136/jmg.11.1.50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Jacobs P. A. Correlation between euploid structural chromosome rearrangements and mental subnormality in humans. Nature. 1974 May 10;249(453):164–165. doi: 10.1038/249164a0. [DOI] [PubMed] [Google Scholar]
  21. Kleczkowska A., Fryns J. P., Standaert L., van den Berghe H. De novo Robertsonian D/D type translocations: the Leuven experience. Clin Genet. 1989 Jul;36(1):65–68. doi: 10.1111/j.1399-0004.1989.tb03368.x. [DOI] [PubMed] [Google Scholar]
  22. Knight L. A., Lipson M., Mann J., Bachman R. Mosaic inversion duplication of chromosome 15 without phenotypic effect: occurrence in a father and daughter. Am J Med Genet. 1984 Mar;17(3):649–654. doi: 10.1002/ajmg.1320170315. [DOI] [PubMed] [Google Scholar]
  23. Koduru P., Chaganti R. Congenital chromosome breakage clusters within Giemsa-light bands and identifies sites of chromatin instability. Cytogenet Cell Genet. 1988;49(4):269–274. doi: 10.1159/000132675. [DOI] [PubMed] [Google Scholar]
  24. MacGregor D. J., Imrie S., Tolmie J. L. Outcome of de novo balanced translocations ascertained prenatally. J Med Genet. 1989 Sep;26(9):590–591. doi: 10.1136/jmg.26.9.590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Miny P., Basaran S., Kuwertz E., Holzgreve W., Pawlowitzki I. H. Inv dup (15): prenatal diagnosis and postnatal follow-up. Prenat Diagn. 1986 Jul-Aug;6(4):303–306. doi: 10.1002/pd.1970060411. [DOI] [PubMed] [Google Scholar]
  26. Mohandas T., Canning N., Chu W., Passage M. B., Anderson C. E., Kaback M. M. Marker chromosomes: cytogenetic characterization and implications for prenatal diagnosis. Am J Med Genet. 1985 Feb;20(2):361–368. doi: 10.1002/ajmg.1320200220. [DOI] [PubMed] [Google Scholar]
  27. Philip N., Mattei M. G., Pellissier M. C., Mattei J. F., Giraud F. Remaniements chromosomiques équilibrés à phénotype anormal. J Genet Hum. 1988 Jan;36(1-2):37–43. [PubMed] [Google Scholar]
  28. Puissant H., Azoulay M., Serre J. L., Piet L. L., Junien C. Molecular analysis of a reciprocal translocation t(5;11) (q11;p13) in a WAGR patient. Hum Genet. 1988 Jul;79(3):280–282. doi: 10.1007/BF00366252. [DOI] [PubMed] [Google Scholar]
  29. Sachs E. S., Van Hemel J. O., Den Hollander J. C., Jahoda M. G. Marker chromosomes in a series of 10,000 prenatal diagnoses. Cytogenetic and follow-up studies. Prenat Diagn. 1987 Feb;7(2):81–89. doi: 10.1002/pd.1970070204. [DOI] [PubMed] [Google Scholar]
  30. Sutherland G. R., Ledbetter D. H. Report of the committee on cytogenetic markers. Cytogenet Cell Genet. 1989;51(1-4):452–458. doi: 10.1159/000132804. [DOI] [PubMed] [Google Scholar]
  31. Sutherland G. R., Simmers R. N. No statistical association between common fragile sites and nonrandom chromosome breakpoints in cancer cells. Cancer Genet Cytogenet. 1988 Mar;31(1):9–15. doi: 10.1016/0165-4608(88)90004-0. [DOI] [PubMed] [Google Scholar]
  32. Therman E., Susman B., Denniston C. The nonrandom participation of human acrocentric chromosomes in Robertsonian translocations. Ann Hum Genet. 1989 Jan;53(Pt 1):49–65. doi: 10.1111/j.1469-1809.1989.tb01121.x. [DOI] [PubMed] [Google Scholar]
  33. Tierney I., Axworthy D., Smith L., Ratcliffe S. G. Balanced rearrangements of the autosomes: results of a longitudinal study of a newborn survey population. J Med Genet. 1984 Feb;21(1):45–51. doi: 10.1136/jmg.21.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Trent J. M., Kaneko Y., Mitelman F. Report of the committee on structural chromosome changes in neoplasia. Cytogenet Cell Genet. 1989;51(1-4):533–562. doi: 10.1159/000132807. [DOI] [PubMed] [Google Scholar]
  35. Van Dyke D. L., Weiss L., Roberson J. R., Babu V. R. The frequency and mutation rate of balanced autosomal rearrangements in man estimated from prenatal genetic studies for advanced maternal age. Am J Hum Genet. 1983 Mar;35(2):301–308. [PMC free article] [PubMed] [Google Scholar]
  36. Wassman E. R., Cheyovich D. L., Nakahara Y. "Possibly" de novo translocations: prenatal risk counseling. Am J Obstet Gynecol. 1989 Sep;161(3):698–702. doi: 10.1016/0002-9378(89)90383-9. [DOI] [PubMed] [Google Scholar]
  37. Wolff F., Schaefer R., Bolte A. Häufigkeit und Bedeutung chromosomaler Translokationen in der pränatalen Diagnostik. Geburtshilfe Frauenheilkd. 1986 Jun;46(6):359–362. doi: 10.1055/s-2008-1035931. [DOI] [PubMed] [Google Scholar]

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

RESOURCES