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Molecular characterisation of a mosaicism with a complex chromosome rearrangement: evidence for coincident chromosome healing by telomere capture and neo-telomere formation
  1. Elyes Chabchoub1,
  2. Laura Rodríguez2,
  3. Enrique Galán3,
  4. Elena Mansilla2,
  5. Maria Luisa Martínez-Fernandez2,
  6. Maria Luisa Martínez-Frías2,
  7. Jean-Pierre Fryns1,
  8. Joris Robert Vermeesch1
  1. 1Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium
  2. 2Estudio Colaborativo Español de Malformaciones Congénitas del Centro de Investigación sobre Anomalías Congénitas, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain
  3. 3Servicio de Pediatría. Hospital Materno Infantil de la seguridad Social de Badajoz, Badajoz, Spain
  1. Correspondence to:
 J R Vermeesch
 Center for Human Genetics, Herestraat 49,3000 Leuven, Belgium; Joris.Vermeesch{at}


Background: Broken chromosomes must acquire new telomeric “caps” to be structurally stable. Chromosome healing can be mediated either by telomerase through neo-telomere synthesis or by telomere capture.

Aim: To unravel the mechanism(s) generating complex chromosomal mosaicisms and healing broken chromosomes.

Methods: G banding, array comparative genomic hybridization (aCGH), fluorescence in-situ hybridisation (FISH) and short tandem repeat analysis (STR) was performed on a girl presenting with mental retardation, facial dysmorphism, urogenital malformations and limb anomalies carrying a complex chromosomal mosaicism.

Results & discussion: The karyotype showed a de novo chromosome rearrangement with two cell lines: one cell line with a deletion 9pter and one cell line carrying an inverted duplication 9p and a non-reciprocal translocation 5pter fragment. aCGH, FISH and STR analysis enabled the deduction of the most likely sequence of events generating this complex mosaic. During embryogenesis, a double-strand break occurred on the paternal chromosome 9. Following mitotic separation of both broken sister chromatids, one acquired a telomere vianeo-telomere formation, while the other generated a dicentric chromosome which underwent breakage during anaphase, giving rise to the del inv dup(9) that was subsequently healed by chromosome 5 telomere capture.

Conclusion: Broken chromosomes can coincidently be rescued by both telomere capture and neo-telomere synthesis.

  • aCGH, array comparative genomic hybridisation
  • BLAST, basic local alignment search tool
  • DSB, double-strand break
  • FISH, fluorescence in situ hybridization
  • LCRs, low-copy repeats

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  • Published Online First 15 December 2006

  • Funding: This work was made possible by grants G.0200.03 from the FWO, OT/O2/40, GOA/2006/12 and Centre of Excellence SymBioSys (Research Council K.U.Leuven EF/05/007), Catholic University of Leuven, and grant (PI020028) from the Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Spain. Elyes Chabchoub was supported by the Ministry of Higher Education from Tunisia (Scholarship 2005-032/001).

  • Competing interests: None.

  • Parental informed consent was obtained for publication of figure 1.