IU Genetic Testing Laboratories, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
IU Genetic Testing Laboratories, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA,
Cytogenet Genome Res. 2020;160(11-12):671-679. doi: 10.1159/000512898. Epub 2021 Feb 3.
Chromoanagenesis, a phenomenon characterized by complex chromosomal rearrangement and reorganization events localized to a limited number of genomic regions, includes the subcategories chromothripsis, chromoanasynthesis, and chromoplexy. Although definitions of these terms are evolving, constitutional chromoanagenesis events have been reported in a limited number of patients with variable phenotypes. We report on 2 cases with complex genomic events characterized by multiple copy number gains and losses confined to a single chromosome region, which are suggestive of constitutional chromoanagenesis. Case 1 is a 43-year-old male with intellectual disability and recently developed generalized tonic-clonic seizures. Chromosomal microarray analysis identified a complex rearrangement involving chromosome region 14q31.1q32.2, consisting of 16 breakpoints ranging in size from 0.2 to 6.2 Mb, with 5 segments of normal copy number present between these alterations. Interestingly, this case represents the oldest known patient with a complex rearrangement indicative of constitutional chromoanagenesis. Case 2 is a 2-year-old female with developmental delay, speech delay, low muscle tone, and seizures. Chromosomal microarray analysis identified a complex rearrangement consisting of 28 breakpoints localized to 18q21.32q23. The size of the copy number alterations ranged from 0.042 to 5.1 Mb, flanked by 12 small segments of normal copy number. These cases add to a growing body of literature demonstrating complex chromosomal rearrangements as a disease mechanism for congenital anomalies.
染色体重组，一种以复杂的染色体重排和重组事件局限于少数基因组区域为特征的现象，包括染色碎裂、染色合成和染色易位等亚类。尽管这些术语的定义还在不断发展，但已在少数具有不同表型的患者中报告了染色体结构重组事件。我们报告了 2 例具有复杂基因组事件的病例，其特征为多个拷贝数增益和缺失局限于单个染色体区域，提示为染色体结构重组。病例 1 是一名 43 岁男性，有智力残疾，最近出现全身性强直阵挛性发作。染色体微阵列分析发现涉及 14q31.1q32.2 染色体区域的复杂重排，由 16 个断点组成，大小从 0.2 到 6.2Mb 不等，这些改变之间有 5 个正常拷贝数的片段。有趣的是，该病例是已知最年长的具有复杂重排提示染色体结构重组的患者。病例 2 是一名 2 岁女性，有发育迟缓、言语迟缓、肌张力低和癫痫发作。染色体微阵列分析发现一个复杂的重排，由 18q21.32q23 上的 28 个断点组成。拷贝数改变的大小从 0.042 到 5.1Mb 不等，两侧有 12 个小的正常拷贝数片段。这些病例增加了越来越多的文献证据，表明复杂的染色体重排是先天性异常的一种疾病机制。
