Skip to main content
NCBI home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 2002 Apr;39(4):266–270. doi: 10.1136/jmg.39.4.266

Automated fluorescent genotyping detects 10% of cryptic subtelomeric rearrangements in idiopathic syndromic mental retardation

M Rio 1, F Molinari 1, S Heuertz 1, C Ozilou 1, P Gosset 1, O Raoul 1, V Cormier-Daire 1, J Amiel 1, S Lyonnet 1, M Le Merrer 1, C Turleau 1, M-C de Blois 1, M Prieur 1, S Romana 1, M Vekemans 1, A Munnich 1, L Colleaux 1
PMCID: PMC1735076  PMID: 11950856

Abstract

Recent studies have shown that cryptic unbalanced subtelomeric rearrangements contribute to a significant proportion of idiopathic syndromic mental retardation cases. Using a fluorescent genotyping based strategy, we found a 10% rate of cryptic subtelomeric rearrangements in a large series of 150 probands with severe idiopathic syndromic mental retardation and normal RHG-GTG banded karyotype. Fourteen children were found to carry deletions or duplications of one or more chromosome telomeres and two children had uniparental disomy. This study clearly shows that fluorescent genotyping is a sensitive and cost effective method that not only detects cryptic subtelomeric rearrangements but also provides a unique opportunity to detect uniparental disomies. We suggest giving consideration to systematic examination of subtelomeric regions in the diagnostic work up of patients with unexplained syndromic mental retardation.

Full Text

The Full Text of this article is available as a PDF (138.1 KB).

Selected References

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

  1. Badge R. M., Yardley J., Jeffreys A. J., Armour J. A. Crossover breakpoint mapping identifies a subtelomeric hotspot for male meiotic recombination. Hum Mol Genet. 2000 May 1;9(8):1239–1244. doi: 10.1093/hmg/9.8.1239. [DOI] [PubMed] [Google Scholar]
  2. Colleaux L., Rio M., Heuertz S., Moindrault S., Turleau C., Ozilou C., Gosset P., Raoult O., Lyonnet S., Cormier-Daire V. A novel automated strategy for screening cryptic telomeric rearrangements in children with idiopathic mental retardation. Eur J Hum Genet. 2001 May;9(5):319–327. doi: 10.1038/sj.ejhg.5200591. [DOI] [PubMed] [Google Scholar]
  3. De Vries B. B., Knight S. J., Homfray T., Smithson S. F., Flint J., Winter R. M. Submicroscopic subtelomeric 1qter deletions: a recognisable phenotype? J Med Genet. 2001 Mar;38(3):175–178. doi: 10.1136/jmg.38.3.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Flint J., Wilkie A. O., Buckle V. J., Winter R. M., Holland A. J., McDermid H. E. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nat Genet. 1995 Feb;9(2):132–140. doi: 10.1038/ng0295-132. [DOI] [PubMed] [Google Scholar]
  5. Ghaffari S. R., Boyd E., Tolmie J. L., Crow Y. J., Trainer A. H., Connor J. M. A new strategy for cryptic telomeric translocation screening in patients with idiopathic mental retardation. J Med Genet. 1998 Mar;35(3):225–233. doi: 10.1136/jmg.35.3.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goodship J., Curtis A., Cross I., Brown J., Emslie J., Wolstenholme J., Bhattacharya S., Burn J. A submicroscopic translocation, t(4;10), responsible for recurrent Wolf-Hirschhorn syndrome identified by allele loss and fluorescent in situ hybridisation. J Med Genet. 1992 Jul;29(7):451–454. [PMC free article] [PubMed] [Google Scholar]
  7. Knight S. J., Horsley S. W., Regan R., Lawrie N. M., Maher E. J., Cardy D. L., Flint J., Kearney L. Development and clinical application of an innovative fluorescence in situ hybridization technique which detects submicroscopic rearrangements involving telomeres. Eur J Hum Genet. 1997 Jan-Feb;5(1):1–8. [PubMed] [Google Scholar]
  8. Knight S. J., Regan R., Nicod A., Horsley S. W., Kearney L., Homfray T., Winter R. M., Bolton P., Flint J. Subtle chromosomal rearrangements in children with unexplained mental retardation. Lancet. 1999 Nov 13;354(9191):1676–1681. doi: 10.1016/S0140-6736(99)03070-6. [DOI] [PubMed] [Google Scholar]
  9. Kuwano A., Ledbetter S. A., Dobyns W. B., Emanuel B. S., Ledbetter D. H. Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization. Am J Hum Genet. 1991 Oct;49(4):707–714. [PMC free article] [PubMed] [Google Scholar]
  10. Lamb J., Wilkie A. O., Harris P. C., Buckle V. J., Lindenbaum R. H., Barton N. J., Reeders S. T., Weatherall D. J., Higgs D. R. Detection of breakpoints in submicroscopic chromosomal translocation, illustrating an important mechanism for genetic disease. Lancet. 1989 Oct 7;2(8667):819–824. doi: 10.1016/s0140-6736(89)92995-4. [DOI] [PubMed] [Google Scholar]
  11. Overhauser J., Bengtsson U., McMahon J., Ulm J., Butler M. G., Santiago L., Wasmuth J. J. Prenatal diagnosis and carrier detection of a cryptic translocation by using DNA markers from the short arm of chromosome 5. Am J Hum Genet. 1989 Aug;45(2):296–303. [PMC free article] [PubMed] [Google Scholar]
  12. Riegel M., Baumer A., Jamar M., Delbecque K., Herens C., Verloes A., Schinzel A. Submicroscopic terminal deletions and duplications in retarded patients with unclassified malformation syndromes. Hum Genet. 2001 Sep;109(3):286–294. doi: 10.1007/s004390100585. [DOI] [PubMed] [Google Scholar]
  13. Rio M., Ozilou C., Cormier-Daire V., Turleau C., Prieur M., Vekemans M., Chauveau P., Munnich A., Colleaux L. Partial maternal heterodisomy of chromosome 17q25 in a case of severe mental retardation. Hum Genet. 2001 Jun;108(6):511–515. doi: 10.1007/s004390100522. [DOI] [PubMed] [Google Scholar]
  14. Roeleveld N., Zielhuis G. A., Gabreëls F. The prevalence of mental retardation: a critical review of recent literature. Dev Med Child Neurol. 1997 Feb;39(2):125–132. doi: 10.1111/j.1469-8749.1997.tb07395.x. [DOI] [PubMed] [Google Scholar]
  15. Rosenberg M. J., Killoran C., Dziadzio L., Chang S., Stone D. L., Meck J., Aughton D., Bird L. M., Bodurtha J., Cassidy S. B. Scanning for telomeric deletions and duplications and uniparental disomy using genetic markers in 120 children with malformations. Hum Genet. 2001 Sep;109(3):311–318. doi: 10.1007/s004390100559. [DOI] [PubMed] [Google Scholar]
  16. Rossi E., Piccini F., Zollino M., Neri G., Caselli D., Tenconi R., Castellan C., Carrozzo R., Danesino C., Zuffardi O. Cryptic telomeric rearrangements in subjects with mental retardation associated with dysmorphism and congenital malformations. J Med Genet. 2001 Jun;38(6):417–420. doi: 10.1136/jmg.38.6.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Slavotinek A., Rosenberg M., Knight S., Gaunt L., Fergusson W., Killoran C., Clayton-Smith J., Kingston H., Campbell R. H., Flint J. Screening for submicroscopic chromosome rearrangements in children with idiopathic mental retardation using microsatellite markers for the chromosome telomeres. J Med Genet. 1999 May;36(5):405–411. [PMC free article] [PubMed] [Google Scholar]
  18. Slavotinek A., Shaffer L. G., Shapira S. K. Monosomy 1p36. J Med Genet. 1999 Sep;36(9):657–663. [PMC free article] [PubMed] [Google Scholar]
  19. Wilkie A. O., Buckle V. J., Harris P. C., Lamb J., Barton N. J., Reeders S. T., Lindenbaum R. H., Nicholls R. D., Barrow M., Bethlenfalvay N. C. Clinical features and molecular analysis of the alpha thalassemia/mental retardation syndromes. I. Cases due to deletions involving chromosome band 16p13.3. Am J Hum Genet. 1990 Jun;46(6):1112–1126. [PMC free article] [PubMed] [Google Scholar]
  20. Wilson L. C., Leverton K., Oude Luttikhuis M. E., Oley C. A., Flint J., Wolstenholme J., Duckett D. P., Barrow M. A., Leonard J. V., Read A. P. Brachydactyly and mental retardation: an Albright hereditary osteodystrophy-like syndrome localized to 2q37. Am J Hum Genet. 1995 Feb;56(2):400–407. [PMC free article] [PubMed] [Google Scholar]
  21. Wong A. C., Ning Y., Flint J., Clark K., Dumanski J. P., Ledbetter D. H., McDermid H. E. Molecular characterization of a 130-kb terminal microdeletion at 22q in a child with mild mental retardation. Am J Hum Genet. 1997 Jan;60(1):113–120. [PMC free article] [PubMed] [Google Scholar]
  22. de Vries B. B., White S. M., Knight S. J., Regan R., Homfray T., Young I. D., Super M., McKeown C., Splitt M., Quarrell O. W. Clinical studies on submicroscopic subtelomeric rearrangements: a checklist. J Med Genet. 2001 Mar;38(3):145–150. doi: 10.1136/jmg.38.3.145. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES