Stabilization of a terminal inversion duplication of 8p by telomere capture from 18q

Terminal inversion duplications of the short arm of chromosome 8 are one of the more common chromosome rearrangements in humans. We report an infant with multiple congenital anomalies, in whom karyotype analysis showed a terminal inversion duplication of 8p including additional material at the distal end of the derivative chromosome, shown to be of chromosome 18q origin. Terminal inversion duplications of 8p are the result of meiotic recombination between inverted olfactory gene receptor repeats in 8p. This recombination generates a dicentric intermediate that breaks during anaphase, and the broken chromosome end is stabilized by telomere healing or telomere capture. The origin of the telomeric region in the majority of constitutional chromosome deletions studied to date was shown to be from telomere healing; the de novo addition of telomeric repeats. In the proband a cytogenetically detectable piece of chromosome 18q was present on the distal end of the derivative 8, suggesting that this chromosome was stabilized by telomere capture of 18q. FISH analyses of additional cases may yield information as to whether telomere capture or telomere-healing events are the predominant mechanism of chromosome stabilization in terminal inversion duplications of 8p.