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Molecular characterization of a mosaicism with a complex chromosome rearrangement: evidence for coincident chromosome healing by telomere capture and neo-telomere formation
  1. Elyes Chabchoub
  1. Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium
    1. Laura Rodríguez
    1. Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud C, Spain
      1. Enrique Galán
      1. Servicio de Pediatría. Hospital Materno Infantil de la seguridad Social de Badajoz, Badajoz, Spain
        1. Elena Mansilla
        1. Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud C, Spain
          1. Maria Luisa Martínez-Fernandez
          1. Centro de Investigación sobre Anomalías Congénitas (CIAC), Instituto de Salud C, Spain
            1. Maria Luisa Martínez-Frías
            1. de Farmacología, Facultad de Medicina, Universidad Complutense. Madrid, Spain
              1. Jean-Pierre Fryns
              1. Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium
                1. Joris R Vermeesch (joris.vermeesch{at}uz.kuleuven.ac.be)
                1. Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium

                  Abstract

                  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), fluorescent in-situ hybridization (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 via neo-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.

                  • array CGH
                  • complex chromosome rearrangement
                  • mosaicism
                  • neo-telomere synthesis
                  • telomere capture

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