Molecular characterisation of a mosaicism with a complex chromosome rearrangement: evidence for coincident chromosome healing by telomere capture and neo-telomere formation.
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.


OBJECTIVE
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.


CONCLUSIONS
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.


CONCLUSIONS
Broken chromosomes can coincidently be rescued by both telomere capture and neo-telomere synthesis.
Chabchoub
Elyes
E
Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.
Rodríguez
Laura
L
Galán
Enrique
E
Mansilla
Elena
E
Martínez-Fernandez
Maria Luisa
ML
Martínez-Frías
Maria Luisa
ML
Fryns
Jean-Pierre
JP
Vermeesch
Joris Robert
JR
D000015:Abnormalities, Multiple / Q000196:embryology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002842:Chromatids / Q000235:genetics / Q000648:ultrastructure; D002871:Chromosome Banding; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000196:embryology / Q000235:genetics*; D007446:Chromosome Inversion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics / Q000648:ultrastructure*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics / Q000648:ultrastructure*; D005260:Female; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000196:embryology / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D018895:Microsatellite Repeats; D009030:Mosaicism; D009693:Nucleic Acid Hybridization; D016615:Telomere / Q000502:physiology*; D014178:Translocation, Genetic