Abstract：
Chromoanagenesis is a phenomenon of highly complex rearrangements involving the massive genomic shattering and reconstitution of chromosomes that has had a great impact on cancer biology and congenital anomalies. Complex chromosomal rearrangements (CCRs) are structural alterations involving three or more chromosomal breakpoints between at least two chromosomes. Here, we present a 3-year-old boy exhibiting multiple congenital malformations and developmental delay. The cytogenetic analysis found a highly complex CCR inherited from the mother involving four chromosomes and five breakpoints due to forming four derivative chromosomes (2, 3, 6 and 11). FISH analysis identified an ultrarare derivative chromosome 11 containing three parts that connected the 11q telomere to partial 6q and 3q fragments. We postulate that this derivative chromosome 11 is associated with chromoanagenesis-like phenomena by which DNA repair can result in a cooccurrence of inter-chromosomal translocations. Additionally, chromosome microarray studies revealed that the child has one subtle maternal-inherited deletion at 6p12.1 and two de novo deletions at 6q14.1 and 6q16.1~6q16.3. Here, we present a familial CCR case with rare rearranged chromosomal structures and the use of multiple molecular techniques to delineate these genomic alterations. We suggest that chromoanagenesis may be a possible mechanism involved in the repair and reconstitution of these rearrangements with evidence for increasing genomic imbalances such as additional deletions in this case.
摘要：
染色体发生是一种高度复杂的重排现象，涉及大量基因组破碎和染色体重建，对癌症生物学和先天性异常产生了巨大影响。复杂染色体重排(CCR)是涉及至少两个染色体之间的三个或更多个染色体断点的结构改变。这里,我们介绍了一个3岁男孩，表现出多种先天性畸形和发育迟缓。细胞遗传学分析发现，由于形成四个衍生染色体（2、3、6和11），从母亲那里继承的高度复杂的CCR涉及四个染色体和五个断点。FISH分析鉴定出了一个ultrarare衍生染色体11，其中包含将11q端粒连接到部分6q和3q片段的三个部分。我们推测，这种衍生的11号染色体与类似显色的现象有关，通过这种现象，DNA修复可以导致染色体间易位的同时发生。此外,染色体微阵列研究显示，该孩子在6p12.1有一个微妙的母体遗传缺失，在6q14.1和6q16.1〜6q16.3有两个从头缺失。这里,我们介绍了一个家族性CCR病例,该病例具有罕见的重排染色体结构,并使用多种分子技术描述了这些基因组改变.我们建议显色诱变可能是这些重排修复和重建的可能机制，有证据表明基因组失衡增加，例如在这种情况下的其他缺失。
