A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements
| العنوان: | A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements |
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| المؤلفون: | Shigeko Satomura, Yuya Ouchi, Masako Saito, Takuya Naruto, Naoko Fujita, Hidehito Inagaki, Hiroki Kurahashi, Chie Murata, Nana Okamoto, Tomohiro Kohmoto, Nobuhiko Okamoto, Kiyoshi Masuda, Issei Imoto |
| المصدر: | Molecular Cytogenetics Molecular Cytogenetics, Vol 10, Iss 1, Pp 1-8 (2017) |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, medicine.medical_specialty, lcsh:QH426-470, Microarray, Breakpoint junction sequence, Case Report, Microhomology-mediated break-induced replication model, Uniparental isodisomy, 030105 genetics & heredity, Biology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Gene duplication, Genetics, medicine, Molecular Biology, Genetics (clinical), Biochemistry (medical), Breakpoint, Cytogenetics, Chromosome, DUP-TRP/INV-DUP structure, 1q, Human genetics, lcsh:Genetics, Template switching, chemistry, Uniparental Isodisomy, Molecular Medicine, Complex genomic rearrangement, Chromosomal microarray, DNA |
| الوصف: | Background Complex genomic rearrangements (CGRs) consisting of interstitial triplications in conjunction with uniparental isodisomy (isoUPD) have rarely been reported in patients with multiple congenital anomalies (MCA)/intellectual disability (ID). One-ended DNA break repair coupled with microhomology-mediated break-induced replication (MMBIR) has been recently proposed as a possible mechanism giving rise to interstitial copy number gains and distal isoUPD, although only a few cases providing supportive evidence in human congenital diseases with MCA have been documented. Case presentation Here, we report on the chromosomal microarray (CMA)-based identification of the first known case with concurrent interstitial duplication at 1q42.12-q42.2 and triplication at 1q42.2-q43 followed by isoUPD for the remainder of chromosome 1q (at 1q43-qter). In distal 1q duplication/triplication overlapping with 1q42.12-q43, variable clinical features have been reported, and our 25-year-old patient with MCA/ID presented with some of these frequently described features. Further analyses including the precise mapping of breakpoint junctions within the CGR in a sequence level suggested that the CGR found in association with isoUPD in our case is a triplication with flanking duplications, characterized as a triplication with a particularly long duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) structure. Because microhomology was observed in both junctions between the triplicated region and the flanking duplicated regions, our case provides supportive evidence for recently proposed replication-based mechanisms, such as MMBIR, underlying the formation of CGRs + isoUPD implicated in chromosomal disorders. Conclusions To the best of our knowledge, this is the first case of CGRs + isoUPD observed in 1q and having DUP-TRP/INV-DUP structure with a long proximal duplication, which supports MMBIR-based model for genomic rearrangements. Molecular cytogenetic analyses using CMA containing single-nucleotide polymorphism probes with further analyses of the breakpoint junctions are recommended in cases suspected of having complex chromosomal abnormalities based on discrepancies between clinical and conventional cytogenetic findings. Electronic supplementary material The online version of this article (doi:10.1186/s13039-017-0316-6) contains supplementary material, which is available to authorized users. |
| وصف الملف: | application/pdf |
| تدمد: | 1755-8166 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e1d69a0ef5655ef054d69a3c8b6f8e0fTest https://doi.org/10.1186/s13039-017-0316-6Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e1d69a0ef5655ef054d69a3c8b6f8e0f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17558166 |
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