Subtelomeric Chromosome Rearrangements in Children with Idiopathic Mental Retardation: Applicability of Three Molecular-cytogenetic Methods

Aim 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. Conclusion Telomere fluorescent in situ hybridization and multiplex ligation-dependent probe amplification are both very useful and interchangeable methods for the 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