title: Detecting rearrangements in children using subtelomeric FISH and SKY.
abstract: The etiology of mental retardation (MR), often presenting as developmental delay in childhood, is unknown in approximately one-half of cases. G-banding is the standard method for investigating those suspected of having a chromosomal etiology; however, detection of structural abnormalities is limited by the size and pattern of the G-bands involved. Rearrangements involving subtelomeric regions have been shown to cause MR and this has generated interest in investigating the prevalence of these rearrangements using telomere-specific probes. In addition, because cryptic interchromosomal rearrangements may not be small or confined to chromosomal ends, spectral karyotyping (SKY) using chromosome-specific painting probes may be of value. We report here a study using these two FISH-based techniques in 50 children with idiopathic MR or developmental delay and normal GTG-banded karyotypes. Our objective was to assess the prevalence of cryptic rearrangements in this population using subtelomeric FISH and SKY. Three rearrangements were detected by subtelomeric FISH: a derivative 5 from a maternal t(5;21); a recombinant 11 from a paternal pericentric inversion; and a 2q deletion that was also present in the mother. Only the derivative 5 was detected by SKY. SKY did not detect any interstitial interchromosomal rearrangement. The prevalence of clinically significant cryptic rearrangements by subtelomeric FISH and SKY was thus 4% (95% confidence interval 0.5-13.7) and 2% (95% CI 0.05-10.7), respectively. This study supports the view that G-banding does not detect all clinically significant chromosomal abnormalities and that subtelomeric FISH and SKY can detect some of these abnormalities.
authors.affiliation: Faculty of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Blaise
authors.initials: B
authors.lastname: Clarkson
authors.forename: Katerina
authors.initials: K
authors.lastname: Pavenski
authors.forename: Lucie
authors.initials: L
authors.lastname: Dupuis
authors.forename: Shelley
authors.initials: S
authors.lastname: Kennedy
authors.forename: Stephen
authors.initials: S
authors.lastname: Meyn
authors.forename: Marjan M
authors.initials: MM
authors.lastname: Nezarati
authors.forename: Gloria
authors.initials: G
authors.lastname: Nie
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
authors.forename: Stephen
authors.initials: S
authors.lastname: Withers
authors.forename: Nada
authors.initials: N
authors.lastname: Quercia
authors.forename: Ahmad S
authors.initials: AS
authors.lastname: Teebi
authors.forename: Ikuko
authors.initials: I
authors.lastname: Teshima
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D020223:Chromosome Painting; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000453:epidemiology / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D009864:Ontario / Q000453:epidemiology