Cryptic genomic imbalances in de novo and inherited apparently balanced chromosomal rearrangements: array CGH study of 47 unrelated cases

Eur J Med Genet. 2009 Sep-Oct;52(5):291-6. doi: 10.1016/j.ejmg.2009.05.011. Epub 2009 Jun 6.


Investigations of apparently balanced chromosomal rearrangements in patients with abnormal phenotype by molecular cytogenetics tools, especially by array CGH, revealed a proportion of unsuspected imbalances. It was estimated recently that 40% of apparently balanced de novo translocations with abnormal phenotype were associated with cryptic deletion. We explored 47 unrelated mental retardation patients carrying an apparently balanced chromosomal rearrangement with high-resolution oligonucleotides arrays. We included 33 de novo cases (21 translocations, 7 inversions and 5 complex chromosomal rearrangements (CCR)) and 14 inherited cases (7 translocations, 5 inversions and 2 CCR). Twenty of the 47 cases (42.6%) carried a cryptic deletion ranging from 60 kb to 15.37 Mb. It concerned 16/33 de novo rearrangements (8/21 translocations, 4/7 inversions and 4/5 CCR) and 4/14 inherited rearrangements (1/7 translocations, 2/5 inversions and 1/2 CCR). The proportion of imbalances was not statistically different between de novo and inherited cases. Our results support that about 40% apparently balanced chromosomal rearrangements with abnormal phenotype are in fact imbalanced and that these rearrangements should be systematically investigated by array CGH independently of their de novo or inherited character.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Chromosome Aberrations* / statistics & numerical data
  • Chromosome Inversion / genetics
  • Chromosome Inversion / statistics & numerical data
  • Comparative Genomic Hybridization*
  • Female
  • Gene Deletion
  • Gene Rearrangement / genetics
  • Genome
  • Humans
  • In Situ Hybridization, Fluorescence
  • Intellectual Disability / genetics*
  • Karyotyping
  • Male
  • Oligonucleotide Array Sequence Analysis*
  • Polymerase Chain Reaction
  • Translocation, Genetic / genetics