The chromosomal region critical in Down syndrome has long been analyzed through genotype–phenotype correlation studies using data from many patients with partial trisomy 21. Owing to that, a relatively small region of human chromosome 21 (35.9 ~ 38.0 Mb) has been considered as Down syndrome critical region (DSCR). In this study, microarray-based comparative genomic hybridization analysis identified complex rearrangements of chromosome 21 in a patient manifesting clinical features partially overlapped with that of Down syndrome. Although the patient did not show up-slanting palpebral fissures and single transverse palmar creases, other symptoms were consistent with Down syndrome. Rearrangements were analyzed by whole-genome sequencing using Nanopore long-read sequencing. The analysis revealed that chromosome 21 was fragmented into seven segments and reassembled by six connected points. Among 12 breakpoints, 5 are located within the short region and overlapped with repeated segments. The rearrangement resulted in a maximum gain of five copies, but no region showed loss of genomic copy numbers. Breakpoint-junctions showed no homologous region. Based on these findings, chromoanasynthesis was considered as the mechanism. Although the distal 21q22.13 region was not included in the aberrant regions, some of the genes located on the duplicated regions, SOD1, SON, ITSN1, RCAN1, and RUNX1, were considered as possible candidate genes for clinical features of the patient. We discussed the critical region for Down syndrome, with the literature review.

长期以来，唐纳德综合征的关键染色体区域已通过基因型与表型相关性研究，使用许多患有21三体性的患者的数据进行了分析，因此，人类21号染色体的相对较小区域（35.9〜38.0 Mb）被认为是唐纳德综合征关键区域（DSCR）。在这项研究中，基于微阵列的比较基因组杂交分析确定了患者的21号染色体的复杂重排，这些患者的临床特征与唐氏综合症的临床特征部分重叠。尽管该患者没有出现上睑裂和单侧掌折痕，但其他症状与唐氏综合症一致。通过使用纳米孔长读测序的全基因组测序分析重排。分析显示，第21号染色体被分成七个部分，并由六个连接点重新组装。在12个断点中，有5个位于短区域内并与重复的段重叠。重排导致最大获得五份拷贝，但是没有区域显示出基因组拷贝数的损失。断点连接处没有显示同源区域。基于这些发现，色合成被认为是机理。尽管21q22.13远端区域未包含在异常区域中，但某些基因位于重复区域中，断点连接处没有显示同源区域。基于这些发现，色合成被认为是机理。尽管21q22.13远端区域未包含在异常区域中，但某些基因位于重复区域中，断点连接处没有显示同源区域。基于这些发现，色合成被认为是机理。尽管21q22.13远端区域未包含在异常区域中，但某些基因位于重复区域中，SOD1，SON，ITSN1，RCAN1和RUNX1被认为是患者临床特征的可能候选基因。我们通过文献综述讨论了唐氏综合症的关键区域。