Subtelomeric rearrangements: results from a study of selected and unselected probands with idiopathic mental retardation and control individuals by using high-resolution G-banding and FISH

Hum Genet. 2001 Oct;109(4):440-51. doi: 10.1007/s004390100588.


The cause of mental retardation, present in approximately 3% of the population, is unexplained in the majority of cases. Recent reports have suggested that cryptic telomeric rearrangements resulting in segmental aneuploidy and gene-dosage imbalance might represent a significant cause of idiopathic mental retardation (IMR). Two groups of patients with unexplained developmental delay (unselected and selected) and a group of control individuals have been investigated to determine the frequency of submicroscopic telomeric rearrangements associated with IMR and the frequency within the normal population. In contrast to current thinking, our data have shown that true cryptic telomeric rearrangements are not a significant cause of IMR. No fully cryptic abnormalities were detected in our IMR groups, although a semi-cryptic unbalanced telomeric translocation was identified in one selected patient by high-resolution G-band analysis. This abnormality was confirmed and characterised by fluorescence in situ hybridisation (FISH) with telomere-specific probes. A further 13 cytogenetically detected subtle terminal rearrangements were characterised by using multi-telomere FISH. Seven of these had previously been reported as normal, three of which were shown to be interstitial deletions. These cases illustrate the importance of high-resolution analysis to exclude subtle but cytogenetically visible abnormalities prior to subtelomere FISH screening when determining the frequency of cryptic telomeric rearrangements. Unexpectedly, two cryptic telomeric abnormalities were detected among our control individuals, suggesting that submicroscopic telomeric abnormalities may be a not uncommon finding in the general population. Hence, our data have important implications when defining the significance of cryptic telomeric rearrangements detected during screening programmes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Chromosome Aberrations*
  • Chromosome Banding / methods*
  • Developmental Disabilities / genetics
  • Ductus Arteriosus, Patent / genetics
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence / methods*
  • Intellectual Disability / genetics*
  • Karyotyping
  • Male
  • Monosomy
  • Phenotype
  • Recombination, Genetic / genetics
  • Sensitivity and Specificity
  • Syndrome
  • Telomere / genetics*
  • Telomere / pathology*
  • Trisomy