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

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.

• Authors: Katsuyuki Yokoi, Yoko Nakajima, Hidehito Inagaki, Makiko Tsutsumi, Tetsuya Ito, Hiroki Kurahashi
• Journal: BMC medical genetics (BMC Med Genet) Vol. 19 Issue 1 Pg. 210 (12 12 2018) ISSN: 1471-2350 [Electronic] England
• PMID: 30541480 (Publication Type: Case Reports, Journal Article)

Chemical References

• OTC protein, human
• Ornithine Carbamoyltransferase

Topics

• Age of Onset
• Base Sequence
• Chromosomes, Human, X (chemistry)
• Exons
• Female
• Gene Duplication
• Gene Expression
• Genes, Recessive
• Humans
• Multiplex Polymerase Chain Reaction
• Ornithine Carbamoyltransferase (genetics, metabolism)
• Ornithine Carbamoyltransferase Deficiency Disease (genetics, metabolism, physiopathology)
• Paternal Inheritance
• Translocation, Genetic
• Young Adult