title: Characterization of terminal chromosome anomalies using multisubtelomere FISH.
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.
authors.affiliation: Cytogenetics Department, Genetics Centre, Guy's & St. Thomas' NHS Trust, London, United Kingdom.
authors.forename: Angela F
authors.initials: AF
authors.lastname: Davies
authors.forename: Toby L
authors.initials: TL
authors.lastname: Kirby
authors.forename: Zoe
authors.initials: Z
authors.lastname: Docherty
authors.forename: Caroline Mackie
authors.initials: CM
authors.lastname: Ogilvie
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D016615:Telomere; D020079:Terminal Repeat Sequences / Q000235:genetics*