The widespread use of genomic copy number analysis has revealed many previously unknown genomic structural variations, including some which are more complex. In this study, three consecutive microdeletions were identified in the same chromosome by microarray-based comparative genomic hybridization (aCGH) analysis for a patient with a neurodevelopmental disorder. Subsequent fluorescence in situ hybridization (FISH) analyses unexpectedly suggested complicated translocations and inversions. For better understanding of the mechanism, breakpoint junctions were analyzed by nanopore sequencing, as a new long-read whole-genome sequencing (WGS) tool. The results revealed a new chromosomal disruption, giving rise to four junctions in chromosome 7. According the sequencing results of breakpoint junctions, all junctions were considered as the consequence of multiple double-strand breaks and the reassembly of DNA fragments by nonhomologous end-joining, indicating chromothripsis. KMT2E, located within the deletion region, was considered as the gene responsible for the clinical features of the patient. Combinatory usage of aCGH and FISH analyses would be recommended for interpretation of structural variations analyzed through WGS.

中文翻译：

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通过纳米孔测序分析复杂基因组重排的断点连接，包括多个连续的微缺失。

基因组拷贝数分析的广泛使用揭示了许多以前未知的基因组结构变异，其中包括一些更复杂的变异。在这项研究中，通过基于微阵列的比较基因组杂交（aCGH）分析，在患有神经发育障碍的患者中，在同一条染色体上鉴定出三个连续的微缺失。随后的荧光原位杂交（FISH）分析意外地表明了复杂的易位和倒位。为了更好地了解该机制，通过纳米孔测序分析了断点连接，这是一种新型的长时全基因组测序（WGS）工具。结果揭示了新的染色体破坏，在7号染色体上产生了四个连接点。根据断点连接点的测序结果，所有连接均被认为是多个双链断裂的结果，并且DNA片段通过非同源末端连接而重新组装，这表明发生了色鳞病。位于缺失区域内的KMT2E被认为是负责患者临床特征的基因。建议将aCGH和FISH分析结合使用，以解释通过WGS分析的结构变异。