Clinical Cytogenetics Laboratory, Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Mol Genet Genomic Med. 2019 Oct;7(10):e00965. doi: 10.1002/mgg3.965. Epub 2019 Sep 2.
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.
Routine cytogenomic analyses and literature review were performed in the study of a case from products of conception (POC).
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.
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.
整合染色体、荧光原位杂交（FISH）和阵列比较基因组杂交（aCGH）分析已被证明在定义不平衡染色体重排方面非常有效。染色体和 aCGH 结果不一致的情况很少见报道。
对来自妊娠产物（POC）的一个病例进行了常规细胞遗传学分析和文献复习。
染色体和 FISH 分析显示一种镶嵌模式，由 5p 的倒位重复的主要异常和随后的 5p 的三次和五次重复分别产生的继发性和三级异常组成。aCGH 分析仅检测到 5p15.33 处 1.521Mb 的末端缺失，基因组中没有其他致病性拷贝数变异。这种镶嵌核型模式可能是体外细胞培养过程中连续的断裂-融合-桥事件诱导的染色体不稳定性所致。对文献的回顾发现，产前和儿科病例中存在 5p 远端缺失和倒位重复的异质性。
这是首例在 POC 中报告的具有独特镶嵌模式和不一致的染色体和 aCGH 结果的病例。在报告和解释这些不一致的结果时应谨慎，并应考虑进一步分析潜在的机制。
