Using SNP array and FISH analysis, a patient with moderate intellectual disability and obesity was found to harbour an atypical 1.6 Mb inverted duplication on 8p23.1, directly flanked by a distally located interstitial deletion of 2.3 Mb and a terminal segmental uniparental disomy. The duplicated and deleted regions lie exactly between the two segmental duplication regions.These segmental duplications on chromosome 8p23.1 are known to be involved in chromosomal rearrangements because of mutual homology and homology to other genomic regions. Genomic instability mediated by these segmental duplications is generally caused by non-allelic homologous recombination, resulting in deletions, reciprocal duplications, inversions and translocations.Additional analysis of the parental origin of the fragments of this atypical inverted duplication/interstitial deletion shows paternal contribution in the maternal derivate chromosome 8. Combined with the finding that the normal chromosome 8 carries an inversion in 8p23.1 we hypothesize that a double strand break in 8p23.1 of the maternal chromosome was postzygotically repaired with the paternal inverted copy resulting in a duplication, deletion and segmental uniparental disomy, with no particular mediation of the 8p23.1 segmental duplication regions in recombination.

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Keywords 8p23.1, BIR, Inv dup del, Olfactory receptor gene cluster, Segmental UPD
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Journal European Journal of Medical Genetics
Knijnenburg, J, Uytdewilligen, M.E.W. (Madiek E.W.), van Hassel, D.A.C.M, Oostenbrink, R, Eussen, H.J.F.M.M, de Klein, A, … van Zutven, L.J.C.M. (2017). Postzygotic telomere capture causes segmental UPD, duplication and deletion of chromosome 8p in a patient with intellectual disability and obesity. European Journal of Medical Genetics, 60(9), 445–450. doi:10.1016/j.ejmg.2017.06.003