PMID- 36292646 OWN - NLM STAT- MEDLINE DCOM- 20221028 LR - 20221108 IS - 2073-4425 (Electronic) IS - 2073-4425 (Linking) VI - 13 IP - 10 DP - 2022 Sep 29 TI - A Central Role of Telomere Dysfunction in the Formation of a Unique Translocation within the Sub-Telomere Region Resulting in Duplication and Partial Trisomy. LID - 10.3390/genes13101762 [doi] LID - 1762 AB - Telomeres play a major role in maintaining genome stability and integrity. Putative involvement of telomere dysfunction in the formation of various types of chromosomal aberrations is an area of active research. Here, we report a case of a six-month-old boy with a chromosomal gain encompassing the 11q22.3q25 region identified by SNP array analysis. The size of the duplication is 26.7 Mb and contains 170 genes (OMIM). The duplication results in partial trisomy of the region in question with clinical consequences, including bilateral renal dysplasia, delayed development, and a heart defect. Moreover, the karyotype determined by R-banding and chromosome painting as well as by hybridization with specific sub-telomere probes revealed the presence of an unbalanced t(9;11)(p24;q22.3) translocation with a unique breakpoint involving the sub-telomere region of the short arm of chromosome 9. The karyotypes of the parents were normal. Telomere integrity in circulating lymphocytes from the child and from his parents was assessed using an automated high-throughput method based on fluorescence in situ hybridization (FISH) with telomere- and centromere-specific PNA probes followed by M-FISH multicolor karyotyping. Very short telomeres, as well as an increased frequency of telomere loss and formation of telomere doublets, were detected in the child's cells. Interestingly, similar telomere profiles were found in the circulating lymphocytes of the father. Moreover, an assessment of clonal telomere aberrations identified chromosomes 9 and 11 with particularly high frequencies of such aberrations. These findings strongly suggest that telomere dysfunction plays a central role in the formation of this specific unbalanced chromosome rearrangement via chromosome end-to-end fusion and breakage-fusion-bridge cycles. FAU - M'Kacher, Radhia AU - M'Kacher R AD - Cell Environment DNA Damage R&D, Genopole, 91058 Evry, France. FAU - Miguet, Marguerite AU - Miguet M AD - Laboratoire de Genetique, Groupe Hospitalier de la Region de Mulhouse Sud-Alsace, 68070 Mulhouse, France. FAU - Maillard, Pierre-Yves AU - Maillard PY AUID- ORCID: 0000-0002-7766-1072 AD - Service de Genetique Hopitaux Universitaires de Strasbourg, Hopital de Haute Pierre, 1, Rue Moliere, 67000 Strasbourg, France. FAU - Colicchio, Bruno AU - Colicchio B AUID- ORCID: 0000-0002-1742-8631 AD - IRIMAS, Institut de Recherche en Informatique, Mathematiques, Automatique et Signal, Universite de Haute-Alsace, 68070 Mulhouse, France. FAU - Scheidecker, Sophie AU - Scheidecker S AD - Laboratoire de Diagnostic Genetique, Hopitaux Universitaires de Strasbourg, Nouvel Hopital Civil, 1, Place de l'Hopital, 67000 Strasbourg, France. FAU - Najar, Wala AU - Najar W AD - Cell Environment DNA Damage R&D, Genopole, 91058 Evry, France. FAU - Arnoux, Micheline AU - Arnoux M AD - APHP-Service d'Hematologie-Oncohematologie Moleculaire et Cytogenetique Hopital Paul Brousse Universite Paris Saclay, 94801 Villejuif, France. FAU - Oudrhiri, Noufissa AU - Oudrhiri N AD - APHP-Service d'Hematologie-Oncohematologie Moleculaire et Cytogenetique Hopital Paul Brousse Universite Paris Saclay, 94801 Villejuif, France. FAU - Borie, Claire AU - Borie C AD - APHP-Service d'Hematologie-Oncohematologie Moleculaire et Cytogenetique Hopital Paul Brousse Universite Paris Saclay, 94801 Villejuif, France. FAU - Biehler, Margaux AU - Biehler M AD - Laboratoire de Diagnostic Genetique, Hopitaux Universitaires de Strasbourg, Nouvel Hopital Civil, 1, Place de l'Hopital, 67000 Strasbourg, France. FAU - Plesch, Andreas AU - Plesch A AD - MetaSystems GmbH, Robert-Bosch-Str. 6, 68804 Altlussheim, Germany. FAU - Heidingsfelder, Leonhard AU - Heidingsfelder L AD - MetaSystems GmbH, Robert-Bosch-Str. 6, 68804 Altlussheim, Germany. FAU - Bennaceur-Griscelli, Annelise AU - Bennaceur-Griscelli A AD - APHP-Service d'Hematologie-Oncohematologie Moleculaire et Cytogenetique Hopital Paul Brousse Universite Paris Saclay, 94801 Villejuif, France. FAU - Dieterlen, Alain AU - Dieterlen A AD - IRIMAS, Institut de Recherche en Informatique, Mathematiques, Automatique et Signal, Universite de Haute-Alsace, 68070 Mulhouse, France. FAU - Voisin, Philippe AU - Voisin P AD - Cell Environment DNA Damage R&D, Genopole, 91058 Evry, France. FAU - Junker, Steffen AU - Junker S AD - Institute of Biomedicine, University of Aarhus, 8000 Aarhus, Denmark. FAU - Carde, Patrice AU - Carde P AD - Department of Hematology Gustave Roussy Cancer Campus, Paris Saclay, 94805 Villejuif, France. FAU - Jeandidier, Eric AU - Jeandidier E AUID- ORCID: 0000-0002-2757-0770 AD - Laboratoire de Genetique, Groupe Hospitalier de la Region de Mulhouse Sud-Alsace, 68070 Mulhouse, France. LA - eng PT - Case Reports PT - Journal Article DEP - 20220929 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 SB - IM MH - Humans MH - *Trisomy/genetics MH - In Situ Hybridization, Fluorescence MH - Chromosome Banding MH - *Translocation, Genetic/genetics MH - Chromosome Aberrations MH - Telomere/genetics PMC - PMC9601474 OTO - NOTNLM OT - chromosomal instability OT - duplication OT - postnatal OT - sub-telomere region OT - telomere OT - trisomy COIS- The authors declare no conflict of interest. EDAT- 2022/10/28 06:00 MHDA- 2022/10/29 06:00 PMCR- 2022/09/29 CRDT- 2022/10/27 01:19 PHST- 2022/08/24 00:00 [received] PHST- 2022/09/22 00:00 [revised] PHST- 2022/09/23 00:00 [accepted] PHST- 2022/10/27 01:19 [entrez] PHST- 2022/10/28 06:00 [pubmed] PHST- 2022/10/29 06:00 [medline] PHST- 2022/09/29 00:00 [pmc-release] AID - genes13101762 [pii] AID - genes-13-01762 [pii] AID - 10.3390/genes13101762 [doi] PST - epublish SO - Genes (Basel). 2022 Sep 29;13(10):1762. doi: 10.3390/genes13101762.