Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 1999 Sep;36(9):694–699.

Molecular characterisation of partial chromosome 21 aneuploidies by fluorescent PCR

R Valero 1, G Marfany 1, R Gil-Benso 1, M d Ibanez 1, I Lopez-Pajares 1, F Prieto 1, G Rullan 1, E Sarret 1, R Gonzalez-Duarte 1
PMCID: PMC1734419  PMID: 10507727

Abstract

Although trisomy of chromosome 21 is the most prevalent human genetic disorder, data from partial 21 aneuploidies are very scanty. Eight different partial aneuploidies for chromosome 21 were characterised by fluorescence quantitative PCR. Allelic dosage analysis was performed for each patient using 25 CHLC STRs covering the entire q arm. The length of the corresponding trisomies and monosomies was ascertained for five partial trisomics and three partial monosomics. All trisomic patients carried unbalanced translocations involving chromosome 21, whereas one of the monosomic patients bore a ring chromosome 21 and another showed an interstitial deletion of chromosome 21. The chromosomal breakpoints of two partial trisomy patients could be clearly delimited. However, the other three trisomies involved most of the 21 q arm as three allelic doses were detected for each marker. Although these latter patients do not show all the features of Down syndrome, genotype/phenotype correlations agree with previously reported data. The chromosomal breakpoints observed in two partially monosomic patients helped further to define the region involved in different phenotypic features associated with chromosome 21 monosomy. Telomeric material loss was also detected in a patient bearing a ring 21 chromosome. The parental origin of the aneuploidy was assigned for each case, which allowed us to conclude that two of the monosomic cases originated from de novo chromosomal rearrangements. There was no correlation with parental sex in contrast to trisomic patients originating from meiotic non-disjunction.


Keywords: Down syndrome; partial trisomy; partial monosomy; chromosome 21

Full Text

The Full Text of this article is available as a PDF (88.8 KB).

Selected References

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

  1. Adinolfi M., Sherlock J., Pertl B. Rapid detection of selected aneuploidies by quantitative fluorescent PCR. Bioessays. 1995 Jul;17(7):661–664. doi: 10.1002/bies.950170712. [DOI] [PubMed] [Google Scholar]
  2. Chettouh Z., Croquette M. F., Delobel B., Gilgenkrants S., Leonard C., Maunoury C., Prieur M., Rethoré M. O., Sinet P. M., Chery M. Molecular mapping of 21 features associated with partial monosomy 21: involvement of the APP-SOD1 region. Am J Hum Genet. 1995 Jul;57(1):62–71. [PMC free article] [PubMed] [Google Scholar]
  3. Dallapiccola B., De Filippis V., Notarangelo A., Perla G., Zelante L. Ring chromosome 21 in healthy persons: different consequences in females and in males. Hum Genet. 1986 Jul;73(3):218–220. doi: 10.1007/BF00401230. [DOI] [PubMed] [Google Scholar]
  4. Delabar J. M., Theophile D., Rahmani Z., Chettouh Z., Blouin J. L., Prieur M., Noel B., Sinet P. M. Molecular mapping of twenty-four features of Down syndrome on chromosome 21. Eur J Hum Genet. 1993;1(2):114–124. doi: 10.1159/000472398. [DOI] [PubMed] [Google Scholar]
  5. Findlay I., Matthews P., Tóth T., Quirke P., Papp Z. Same day diagnosis of Down's syndrome and sex in single cells using multiplex fluorescent PCR. Mol Pathol. 1998 Jun;51(3):164–167. doi: 10.1136/mp.51.3.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hubert R. S., Mitchell S., Chen X. N., Ekmekji K., Gadomski C., Sun Z., Noya D., Kim U. J., Chen C., Shizuya H. BAC and PAC contigs covering 3.5 Mb of the Down syndrome congenital heart disease region between D21S55 and MX1 on chromosome 21. Genomics. 1997 Apr 15;41(2):218–226. doi: 10.1006/geno.1997.4657. [DOI] [PubMed] [Google Scholar]
  7. Jackson J. F., North E. R., 3rd, Thomas J. G. Clinical diagnosis of Down's syndrome. Clin Genet. 1976 May;9(5):483–487. doi: 10.1111/j.1399-0004.1976.tb01601.x. [DOI] [PubMed] [Google Scholar]
  8. Kleczkowska A., Fryns J. P. Ring chromosome 21 in a normal female. Ann Genet. 1984;27(2):126–128. [PubMed] [Google Scholar]
  9. Korenberg J. R., Chen X. N., Schipper R., Sun Z., Gonsky R., Gerwehr S., Carpenter N., Daumer C., Dignan P., Disteche C. Down syndrome phenotypes: the consequences of chromosomal imbalance. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4997–5001. doi: 10.1073/pnas.91.11.4997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Korenberg J. R., Kalousek D. K., Anneren G., Pulst S. M., Hall J. G., Epstein C. J., Cox D. R. Deletion of chromosome 21 and normal intelligence: molecular definition of the lesion. Hum Genet. 1991 Jun;87(2):112–118. doi: 10.1007/BF00204163. [DOI] [PubMed] [Google Scholar]
  11. Kucerová M., Polívková Z. A case of a girl with a 21 ring chromosome. Hum Hered. 1974;24(1):100–104. doi: 10.1159/000152643. [DOI] [PubMed] [Google Scholar]
  12. Mansfield E. S. Diagnosis of Down syndrome and other aneuploidies using quantitative polymerase chain reaction and small tandem repeat polymorphisms. Hum Mol Genet. 1993 Jan;2(1):43–50. doi: 10.1093/hmg/2.1.43. [DOI] [PubMed] [Google Scholar]
  13. McGinniss M. J., Kazazian H. H., Jr, Stetten G., Petersen M. B., Boman H., Engel E., Greenberg F., Hertz J. M., Johnson A., Laca Z. Mechanisms of ring chromosome formation in 11 cases of human ring chromosome 21. Am J Hum Genet. 1992 Jan;50(1):15–28. [PMC free article] [PubMed] [Google Scholar]
  14. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Orr-Weaver T. Meiotic nondisjunction does the two-step. Nat Genet. 1996 Dec;14(4):374–376. doi: 10.1038/ng1296-374. [DOI] [PubMed] [Google Scholar]
  16. Orti R., Mégarbane A., Maunoury C., Van Broeckhoven C., Sinet P. M., Delabar J. M. High-resolution physical mapping of a 6.7-Mb YAC contig spanning a region critical for the monosomy 21 phenotype in 21q21.3-q22.1. Genomics. 1997 Jul 1;43(1):25–33. doi: 10.1006/geno.1997.4765. [DOI] [PubMed] [Google Scholar]
  17. Pertl B., Weitgasser U., Kopp S., Kroisel P. M., Sherlock J., Adinolfi M. Rapid detection of trisomies 21 and 18 and sexing by quantitative fluorescent multiplex PCR. Hum Genet. 1996 Jul;98(1):55–59. doi: 10.1007/s004390050159. [DOI] [PubMed] [Google Scholar]
  18. Prieto F., Badia L., Asensi F., Roques V. Two reciprocal translocations t(9p+;13q-) and t(13q-;21q+): a study of the families. Hum Genet. 1980;54(1):7–11. doi: 10.1007/BF00279042. [DOI] [PubMed] [Google Scholar]
  19. Richer C. L., Fitch N., Sitahal S., Murer-Orlando M., Jean P. Analysis of banding patterns in a case of ring chromosome 21. Am J Med Genet. 1981;10(4):323–331. doi: 10.1002/ajmg.1320100404. [DOI] [PubMed] [Google Scholar]
  20. Schmid W., Tenconi R., Baccichetti C., Caufin D., Schinzel A. Ring chromosome 21 in phenotypically apparently normal persons: report of two families from Switzerland and Italy. Am J Med Genet. 1983 Nov;16(3):323–329. doi: 10.1002/ajmg.1320160305. [DOI] [PubMed] [Google Scholar]
  21. von Eggeling F., Freytag M., Fahsold R., Horsthemke B., Claussen U. Rapid detection of trisomy 21 by quantitative PCR. Hum Genet. 1993 Jul;91(6):567–570. doi: 10.1007/BF00205081. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES