title: Application of molecular cytogenetic techniques to clarify apparently balanced complex chromosomal rearrangements in two patients with an abnormal phenotype: case report.
abstract: BACKGROUND
  Complex chromosomal rearrangements (CCR) are rare cytogenetic findings that are difficult to karyotype by conventional cytogenetic analysis partially because of the relative low resolution of this technique. High resolution genotyping is necessary in order to identify cryptic imbalances, for instance near the multiple breakpoints, to explain the abnormal phenotype in these patients. We applied several molecular techniques to elucidate the complexity of the CCRs of two adult patients with abnormal phenotypes.
  
  
  RESULTS
  Multicolour fluorescence in situ hybridization (M-FISH) showed that in patient 1 the chromosomes 1, 10, 15 and 18 were involved in the rearrangement whereas for patient 2 the chromosomes 5, 9, 11 and 13 were involved. A 250 k Nsp1 SNP-array analysis uncovered a deletion in chromosome region 10p13 for patient 1, harbouring 17 genes, while patient 2 showed no pathogenic gains or losses. Additional FISH analysis with locus specific BAC-probes was performed, leading to the identification of cryptic interstitial structural rearrangements in both patients.
  
  
  CONCLUSIONS
  Application of M-FISH and SNP-array analysis to apparently balanced CCRs is useful to delineate the complex chromosomal rearrangement in detail. However, it does not always identify cryptic imbalances as an explanation for the abnormal phenotype in patients with a CCR.
authors: Department of Clinical Genetics, Erasmus MC, Rotterdam, the Netherlands. p.j.poddighe@erasmusmc.nl.
authors: Paula Jp
authors: PJ
authors: de Vree
authors: Marleen Eh
authors: ME
authors: Simon
authors: Marieke F
authors: MF
authors: van Dooren
authors: Gerda Ht
authors: GH
authors: Stoevelaar
authors: José Tw
authors: JT
authors: Hilkmann
authors: Michel A
authors: MA
authors: Rongen
authors: Gido Cm
authors: GC
authors: Huijbregts
authors: Annemieke Jmh
authors: AJ
authors: Verkerk
authors: Pino J
authors: PJ
authors: Poddighe