Subtelomeric chromosome rearrangements in children with idiopathic mental retardation: applicability of three molecular-cytogenetic methods.
OBJECTIVE
To identify cryptic subtelomeric rearrangement, a possible cause of idiopathic mental retardation by means of multiprobe telomere fluorescent in situ hybridization (T-FISH).


METHODS
Hundred patients (median age 3.0 years) with mental retardation and dysmorphic features were screened using specific T-FISH probes. Multiplex ligation-dependent probe amplification and comparative genomic hybridization were used for the confirmation of results.


RESULTS
Telomere fluorescent in situ hybridization revealed 11 subtelomeric abnormalities in 10 patients (10%; 95% CI, 5.0-17.5). Four of these had only a deletion of subtelomere 2q, which was apparently a normal variant. Among 6 true aberrations (6%; 95% CI, 2.5-12.5) we found 2 de novo subtelomeric deletions and 4 unbalanced subtelomeric rearrangements (one de novo). All clinically significant subtelomeric rearrangements were confirmed by multiplex ligation-dependent probe amplification. Comparative genomic hybridization was used to investigate the whole genome of patients in whom a subtelomeric anomaly was found, confirming some, but not all subtelomeric rearrangements.


CONCLUSIONS
Telomere fluorescent in situ hybridization and multiplex ligation-dependent probe amplification are both very useful and interchangeable methods for detection of unbalanced chromosome rearrangements, but T-FISH also detects balanced rearrangements. In our experiment the resolution power of comparative genomic hybridization was too low for subtelomeric screening compared with T-FISH and multiplex ligation-dependent probe amplification.
Erjavec-Skerget
Alenka
A
Medical Genetics Laboratory, Maribor Teaching Hospital, Maribor, Slovenia. alenka.erjavec@sb-mb.si
Stangler-Herodez
Spela
S
Zagorac
Andreja
A
Zagradisnik
Boris
B
Kokalj-Vokac
Nadja
N
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D016615:Telomere / Q000235:genetics*