A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements

• Kohmoto, Tomohiro

• Okamoto, Nana

• Naruto, Takuya

• Murata, Chie

• Ouchi, Yuya

• Fujita, Naoko

• Inagaki, Hidehito

• Satomura, Shigeko

• Okamoto, Nobuhiko

• Saito, Masako

• Masuda, Kiyoshi

• Kurahashi, Hiroki

• Imoto, Issei

抄録

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.

収録刊行物

• Molecular Cytogenetics

  Molecular Cytogenetics 10 15-, 2017-04-28

  BioMed Central|Springer Nature

キーワード

• 1q
• Complex genomic rearrangement
• Uniparental isodisomy
• DUP-TRP/INV-DUP structure
• Microhomology-mediated break-induced replication model
• Template switching
• Chromosomal microarray
• Breakpoint junction sequence

詳細情報

• CRID: 1050567903550127488
• NII論文ID: 120006937633
• ISSN: 17558166
• DOI: 10.1186/s13039-017-0316-6
• Web Site: https://repo.lib.tokushima-u.ac.jp/114523
• Web Site: http://link.springer.com/content/pdf/10.1186/s13039-017-0316-6.pdf
• Web Site: http://link.springer.com/article/10.1186/s13039-017-0316-6/fulltext.html
• 本文言語コード: en
• 資料種別: journal article
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