Characterization of terminal chromosome anomalies using multisubtelomere FISH

Am J Med Genet A. 2003 Aug 1;120A(4):483-9. doi: 10.1002/ajmg.a.20056.

Abstract

Telomeric repeat sequences (TTAGGG) are known to cap the termini of every human chromosome. Proximal to these repeat sequences are chromosome-specific repeat sequences, which in turn are distal to gene-rich regions. Submicroscopic, subtle, or cryptic abnormalities in these regions can now be investigated using commercial probe sets for all of the chromosome-specific subtelomeric regions of the human genome. Using this technology, previously unidentified genomic imbalance has been found in a proportion of patients with idiopathic developmental delay and learning difficulties. We have used these probe sets to investigate cases with apparently terminal anomalies detected on G-banded chromosome analysis. As a result of such investigations, we have found that 3 (19%) of 16 apparently terminal deletion cases were the result of more complex rearrangements involving other chromosome subtelomeres. The remaining 13 cases contained no chromosome-specific subtelomere repeats on the deleted arm, but in all 16 cases, the TTAGGG telomere repeat cap was present. A further case was investigated where extra material was found in the terminal region of the chromosome 12 short arm, found to represent a complex inversion/duplication/deletion rearrangement. Investigation of all cases with terminal anomalies, including apparently terminal deletions, is likely to uncover further cases involving complex rearrangements and should lead to a greater understanding of the mechanisms by which these abnormalities arise.

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Chromosome Aberrations*
  • Chromosome Deletion
  • Humans
  • In Situ Hybridization, Fluorescence / methods*
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Telomere*
  • Terminal Repeat Sequences* / genetics*