Parental origin of deletions and duplications – about the necessity to check for cryptic inversions
Abstract 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...
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doaj-2f1d056e4fde486589670468907f3f982020-11-25T00:31:05ZengBMCMolecular Cytogenetics1755-81662018-03-011111810.1186/s13039-018-0369-1Parental origin of deletions and duplications – about the necessity to check for cryptic inversionsThomas Liehr0Isolde Schreyer1Alma Kuechler2Emmanouil Manolakos3Sylke Singer4Andreas Dufke5Kathleen Wilhelm6Tereza Jančušková7Radek Čmejla8Moneeb A. K. Othman9Ahmed H. Al-Rikabi10Kristin Mrasek11Monika Ziegler12Stefanie Kankel13Katharina Kreskowski14Anja Weise15Jena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversityJena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversityInstitut für Humangenetik, Universitätsklinikum EssenAccess to Genome, ATG LabsInstitut für Medizinische Genetik und angewandte GenomikInstitut für Medizinische Genetik und angewandte GenomikJena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversitySynlab czech s.r.o., synlab genetics s.r.oSynlab czech s.r.o., synlab genetics s.r.oJena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversityJena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversityJena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversityJena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversityJena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversityJena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversityJena University Hospital, Institute of Human Genetics, Friedrich Schiller UniversityAbstract 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.http://link.springer.com/article/10.1186/s13039-018-0369-1Copy number variants (CNVs)Microdeletion/microduplication syndromes (MMSs)Three color fluorescence in situ hybridization (FISH)InversionDeletionDuplication |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Thomas Liehr Isolde Schreyer Alma Kuechler Emmanouil Manolakos Sylke Singer Andreas Dufke Kathleen Wilhelm Tereza Jančušková Radek Čmejla Moneeb A. K. Othman Ahmed H. Al-Rikabi Kristin Mrasek Monika Ziegler Stefanie Kankel Katharina Kreskowski Anja Weise |
spellingShingle |
Thomas Liehr Isolde Schreyer Alma Kuechler Emmanouil Manolakos Sylke Singer Andreas Dufke Kathleen Wilhelm Tereza Jančušková Radek Čmejla Moneeb A. K. Othman Ahmed H. Al-Rikabi Kristin Mrasek Monika Ziegler Stefanie Kankel Katharina Kreskowski Anja Weise Parental origin of deletions and duplications – about the necessity to check for cryptic inversions Molecular Cytogenetics Copy number variants (CNVs) Microdeletion/microduplication syndromes (MMSs) Three color fluorescence in situ hybridization (FISH) Inversion Deletion Duplication |
author_facet |
Thomas Liehr Isolde Schreyer Alma Kuechler Emmanouil Manolakos Sylke Singer Andreas Dufke Kathleen Wilhelm Tereza Jančušková Radek Čmejla Moneeb A. K. Othman Ahmed H. Al-Rikabi Kristin Mrasek Monika Ziegler Stefanie Kankel Katharina Kreskowski Anja Weise |
author_sort |
Thomas Liehr |
title |
Parental origin of deletions and duplications – about the necessity to check for cryptic inversions |
title_short |
Parental origin of deletions and duplications – about the necessity to check for cryptic inversions |
title_full |
Parental origin of deletions and duplications – about the necessity to check for cryptic inversions |
title_fullStr |
Parental origin of deletions and duplications – about the necessity to check for cryptic inversions |
title_full_unstemmed |
Parental origin of deletions and duplications – about the necessity to check for cryptic inversions |
title_sort |
parental origin of deletions and duplications – about the necessity to check for cryptic inversions |
publisher |
BMC |
series |
Molecular Cytogenetics |
issn |
1755-8166 |
publishDate |
2018-03-01 |
description |
Abstract 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. |
topic |
Copy number variants (CNVs) Microdeletion/microduplication syndromes (MMSs) Three color fluorescence in situ hybridization (FISH) Inversion Deletion Duplication |
url |
http://link.springer.com/article/10.1186/s13039-018-0369-1 |
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