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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 2000 Apr 19;66(6):1787–1793. doi: 10.1086/302916

Identification of uniparental disomy following prenatal detection of Robertsonian translocations and isochromosomes.

S A Berend 1, J Horwitz 1, C McCaskill 1, L G Shaffer 1
PMCID: PMC1378034  PMID: 10775524

Abstract

Rearrangements of the acrocentric chromosomes (Robertsonian translocations and isochromosomes) are associated with an increased risk of aneuploidy. Given this, and the large number of reported cases of uniparental disomy (UPD) associated with an acrocentric rearrangement, carriers are presumed to be at risk for UPD. However, an accurate risk estimate for UPD associated with these rearrangements is lacking. A total of 174 prenatally identified acrocentric rearrangements, including both Robertsonian translocations and isochromosomes, were studied prospectively to identify UPD for the chromosomes involved in the rearrangements. The overall goal of the study was to provide an estimate of the risk of UPD associated with nonhomologous Robertsonian translocations and homologous acrocentric rearrangements. Of the 168 nonhomologous Robertsonian translocations studied, one showed UPD for chromosome 13, providing a risk estimate of 0.6%. Four of the six homologous acrocentric rearrangements showed UPD, providing a risk estimate of 66%. These cases have also allowed delineation of the mechanisms involved in producing UPD unique to Robertsonian translocations. Given the relatively high risk for UPD in prenatally identified Robertsonian translocations and isochromosomes, UPD testing should be considered, especially for cases involving the acrocentric chromosomes 14 and 15, in which UPD is associated with adverse clinical outcomes.

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Selected References

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  1. Berend S. A., Feldman G. L., McCaskill C., Czarnecki P., Van Dyke D. L., Shaffer L. G. Investigation of two cases of paternal disomy 13 suggests timing of isochromosome formation and mechanisms leading to uniparental disomy. Am J Med Genet. 1999 Jan 29;82(3):275–281. doi: 10.1002/(sici)1096-8628(19990129)82:3<275::aid-ajmg15>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
  2. Cassidy S. B., Lai L. W., Erickson R. P., Magnuson L., Thomas E., Gendron R., Herrmann J. Trisomy 15 with loss of the paternal 15 as a cause of Prader-Willi syndrome due to maternal disomy. Am J Hum Genet. 1992 Oct;51(4):701–708. [PMC free article] [PubMed] [Google Scholar]
  3. Cheung S. W., Shaffer L. G., Richards C. S., Page S. L., Riconda D. L. Prenatal diagnosis of a fetus with a homologous Robertsonian translocation of chromosomes 15. Am J Med Genet. 1997 Oct 3;72(1):47–50. doi: 10.1002/(sici)1096-8628(19971003)72:1<47::aid-ajmg10>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  4. Engel E. A new genetic concept: uniparental disomy and its potential effect, isodisomy. Am J Med Genet. 1980;6(2):137–143. doi: 10.1002/ajmg.1320060207. [DOI] [PubMed] [Google Scholar]
  5. Hamerton J. L., Canning N., Ray M., Smith S. A cytogenetic survey of 14,069 newborn infants. I. Incidence of chromosome abnormalities. Clin Genet. 1975 Oct;8(4):223–243. doi: 10.1111/j.1399-0004.1975.tb01498.x. [DOI] [PubMed] [Google Scholar]
  6. Han J. Y., Choo K. H., Shaffer L. G. Molecular cytogenetic characterization of 17 rob(13q14q) Robertsonian translocations by FISH, narrowing the region containing the breakpoints. Am J Hum Genet. 1994 Nov;55(5):960–967. [PMC free article] [PubMed] [Google Scholar]
  7. Harris D. J., Hankins L., Begleiter M. L. Reproductive risk of t(13q14q) carriers: case report and review. Am J Med Genet. 1979;3(2):175–181. doi: 10.1002/ajmg.1320030208. [DOI] [PubMed] [Google Scholar]
  8. Hook E. B. Exclusion of chromosomal mosaicism: tables of 90%, 95% and 99% confidence limits and comments on use. Am J Hum Genet. 1977 Jan;29(1):94–97. [PMC free article] [PubMed] [Google Scholar]
  9. Koehler K. E., Hawley R. S., Sherman S., Hassold T. Recombination and nondisjunction in humans and flies. Hum Mol Genet. 1996;5(Spec No):1495–1504. doi: 10.1093/hmg/5.supplement_1.1495. [DOI] [PubMed] [Google Scholar]
  10. Kotzot D. Abnormal phenotypes in uniparental disomy (UPD): fundamental aspects and a critical review with bibliography of UPD other than 15. Am J Med Genet. 1999 Jan 29;82(3):265–274. [PubMed] [Google Scholar]
  11. Lai E. C., Kao F. T., Law M. L., Woo S. L. Assignment of the alpha 1-antitrypsin gene and a sequence-related gene to human chromosome 14 by molecular hybridization. Am J Hum Genet. 1983 May;35(3):385–392. [PMC free article] [PubMed] [Google Scholar]
  12. Ledbetter D. H., Engel E. Uniparental disomy in humans: development of an imprinting map and its implications for prenatal diagnosis. Hum Mol Genet. 1995;4(Spec No):1757–1764. doi: 10.1093/hmg/4.suppl_1.1757. [DOI] [PubMed] [Google Scholar]
  13. Mares A., Jr, Ledbetter S. A., Ledbetter D. H., Roberts R., Hejtmancik J. F. Isolation of a human chromosome 14-only somatic cell hybrid: analysis using Alu and LINE-based PCR. Genomics. 1991 Sep;11(1):215–218. doi: 10.1016/0888-7543(91)90122-u. [DOI] [PubMed] [Google Scholar]
  14. Neri G., Serra A., Campana M., Tedeschi B. Reproductive risks for translocation carriers: cytogenetic study and analysis of pregnancy outcome in 58 families. Am J Med Genet. 1983 Dec;16(4):535–561. doi: 10.1002/ajmg.1320160412. [DOI] [PubMed] [Google Scholar]
  15. Page S. L., Shin J. C., Han J. Y., Choo K. H., Shaffer L. G. Breakpoint diversity illustrates distinct mechanisms for Robertsonian translocation formation. Hum Mol Genet. 1996 Sep;5(9):1279–1288. doi: 10.1093/hmg/5.9.1279. [DOI] [PubMed] [Google Scholar]
  16. Robinson W. P., Bernasconi F., Dutly F., Lefort G., Romain D. R., Binkert F., Schinzel A. A. Molecular studies of translocations and trisomy involving chromosome 13. Am J Med Genet. 1996 Jan 11;61(2):158–163. doi: 10.1002/(SICI)1096-8628(19960111)61:2<158::AID-AJMG11>3.0.CO;2-T. [DOI] [PubMed] [Google Scholar]
  17. Robinson W. P., Langlois S., Schuffenhauer S., Horsthemke B., Michaelis R. C., Christian S., Ledbetter D. H., Schinzel A. Cytogenetic and age-dependent risk factors associated with uniparental disomy 15. Prenat Diagn. 1996 Sep;16(9):837–844. doi: 10.1002/(SICI)1097-0223(199609)16:9<837::AID-PD956>3.0.CO;2-7. [DOI] [PubMed] [Google Scholar]
  18. Shaffer L. G., McCaskill C., Adkins K., Hassold T. J. Systematic search for uniparental disomy in early fetal losses: the results and a review of the literature. Am J Med Genet. 1998 Oct 12;79(5):366–372. [PubMed] [Google Scholar]
  19. Shaffer L. G., McCaskill C., Haller V., Brown J. A., Jackson-Cook C. K. Further characterization of 19 cases of rea(21q21q) and delineation as isochromosomes or Robertsonian translocations in Down syndrome. Am J Med Genet. 1993 Dec 1;47(8):1218–1222. doi: 10.1002/ajmg.1320470818. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Spence J. E., Perciaccante R. G., Greig G. M., Willard H. F., Ledbetter D. H., Hejtmancik J. F., Pollack M. S., O'Brien W. E., Beaudet A. L. Uniparental disomy as a mechanism for human genetic disease. Am J Hum Genet. 1988 Feb;42(2):217–226. [PMC free article] [PubMed] [Google Scholar]
  23. Sullivan B. A., Jenkins L. S., Karson E. M., Leana-Cox J., Schwartz S. Evidence for structural heterogeneity from molecular cytogenetic analysis of dicentric Robertsonian translocations. Am J Hum Genet. 1996 Jul;59(1):167–175. [PMC free article] [PubMed] [Google Scholar]
  24. 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]

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