Parental origin of deletions and duplications - about the necessity to check for cryptic inversions.

Autor: Liehr T; 1Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Postfach D-07740, Jena, Germany., Schreyer I; 1Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Postfach D-07740, Jena, Germany.; 2Center for Ambulant Medicine, Jena University Hospital, Jena, Germany., Kuechler A; 3Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany., Manolakos E; Access to Genome, ATG Labs, Athens, Greece., Singer S; Institut für Medizinische Genetik und angewandte Genomik, Tübingen, Germany., Dufke A; Institut für Medizinische Genetik und angewandte Genomik, Tübingen, Germany., Wilhelm K; 1Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Postfach D-07740, Jena, Germany., Jančušková T; 6Synlab czech s.r.o., synlab genetics s.r.o, Praha, Czech Republic., Čmejla R; 6Synlab czech s.r.o., synlab genetics s.r.o, Praha, Czech Republic., Othman MAK; 1Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Postfach D-07740, Jena, Germany., Al-Rikabi AH; 1Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Postfach D-07740, Jena, Germany., Mrasek K; 1Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Postfach D-07740, Jena, Germany., Ziegler M; 1Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Postfach D-07740, Jena, Germany., Kankel S; 1Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Postfach D-07740, Jena, Germany., Kreskowski K; 1Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Postfach D-07740, Jena, Germany., Weise A; 1Jena University Hospital, Institute of Human Genetics, Friedrich Schiller University, Postfach D-07740, Jena, Germany.
Jazyk: angličtina
Zdroj: Molecular cytogenetics [Mol Cytogenet] 2018 Mar 09; Vol. 11, pp. 20. Date of Electronic Publication: 2018 Mar 09 (Print Publication: 2018).
DOI: 10.1186/s13039-018-0369-1
Abstrakt: Background: Copy number variants (CNVs) are the genetic bases for microdeletion/ microduplication syndromes (MMSs). Couples with an affected child and desire to have further children are routinely tested for a potential parental origin of a specific CNV either by molecular karyotyping or by two color fluorescence in situ hybridization (FISH), yet. In the latter case a critical region probe (CRP) is combined with a control probe for identification of the chromosome in question. However, CNVs can arise also due to other reasons, like a recombination-event based on a submicroscopic, cryptic inversion in one of the parents.
Results: Seventy-four patients with different MMSs and overall 81 CNVs were studied here by a novel three color FISH approach. The way how three locus-specific probes are selected (one is the CRP and two are flanking it in a distance of 5-10 Mb) enables to detect or exclude two possible parental conditions as origins of the CNV seen in the index: (i) direct parental origin of the CNV (deletion or duplication) or (ii) a parental cryptic inversion. Thus, for overall 51/81 CNVs (63%) a parental origin could be determined. 36/51 (70.5%) inherited the CNV directly from one of the parents, but 15/51 (29.5%) were due to an exclusively by three color FISH detectable parental inversion. A 2:1 ratio of maternal versus paternal inheritance was found. Also almost two times more male than female were among the index patients.
Conclusion: The new, here suggested three color FISH approach is suited for more comprehensive parental studies of patients with MMS. The detection rate for parental origin was increased by 140% in this study. Still, for 30/81 cases (37%) no reason for the 'de novo' MMS in the affected index patient could be found by the here suggested FISH-probe set.
Competing Interests: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national). Ethics committee of University Clinic Jena approved the study (2303-05/08).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Databáze: MEDLINE
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