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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2018

Open Access 01-12-2018 | Case report

Exonic duplication of the OTC gene by a complex rearrangement that likely occurred via a replication-based mechanism: a case report

Authors: Katsuyuki Yokoi, Yoko Nakajima, Hidehito Inagaki, Makiko Tsutsumi, Tetsuya Ito, Hiroki Kurahashi

Published in: BMC Medical Genetics | Issue 1/2018

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Abstract

Background

Ornithine transcarbamylase deficiency (OTCD) is an X-linked recessive disorder involving a defect in the urea cycle caused by OTC gene mutations. Although a total of 417 disease-causing mutations in OTC have been reported, structural abnormalities in this gene are rare. We here describe a female OTCD case caused by an exonic duplication of the OTC gene (exons 1–6).

Case presentation

A 23-year-old woman with late-onset OTCD diagnosed by biochemical testing was subjected to subsequent genetic testing. Sanger sequencing revealed no pathogenic mutation throughout the coding exons of the OTC gene, but multiplex ligation-dependent probe amplification (MLPA) revealed duplication of exons 1–6. Further genetic analyses revealed an inversion of duplicated exon 1 and a tandem duplication of exons 2–6. Each of the junctions of the inversion harbored a microhomology and non-templated microinsertion, respectively, suggesting a replication-based mechanism. The duplication was also of de novo origin but segregation analysis indicated that it took place in the paternal chromosome.

Conclusion

We report the first OTCD case harboring an exonic duplication in the OTC gene. The functional defects caused by this anomaly were determined via structural analysis of its complex rearrangements.
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Metadata
Title
Exonic duplication of the OTC gene by a complex rearrangement that likely occurred via a replication-based mechanism: a case report
Authors
Katsuyuki Yokoi
Yoko Nakajima
Hidehito Inagaki
Makiko Tsutsumi
Tetsuya Ito
Hiroki Kurahashi
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-018-0733-3

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