Inverted duplication, triplication and quintuplication through sequential breakage-fusion-bridge events induced by a terminal deletion at 5p in a case of spontaneous abortion

Abstract

Background: Integrated chromosome, fluorescence in situ hybridization (FISH) and array comparative genomic hybridization (aCGH) analyses have been effective in defining unbalanced chromosomal rearrangements. Discordant chromosome and aCGH results are rarely reported. Methods: Routine cytogenomic analyses and literature review were performed in the study of a case from products of conception (POC). Results: Chromosome and FISH analysis revealed a mosaic pattern consisting of a primary aberration of an inverted duplication of 5p and derived secondary and tertiary aberrations from sequential triplication and quintuplication of 5p, respectively. The aCGH analysis detected only a 1.521 Mb terminal deletion at 5p15.33 with no other pathogenic copy number variants in the genome. This mosaic karyotypic pattern likely resulted from chromosome instability induced by sequential breakage-fusion-bridge events during in vitro cell culture. A review of literature found heterogeneous distal deletion and inverted duplication of 5p in prenatal and pediatric cases. Conclusion: This is the first case reported in POC with a unique mosaic pattern and discordant chromosome and aCGH results. Caution should be applied in reporting and interpreting these discordant results and further analysis for underlying mechanism should be considered.