Balow Stephanie A, Coyan Alyxis G, Smith Nicki, Russell Bianca E, Monteil Danielle, Hopkin Robert J, Smolarek Teresa A
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Mol Cytogenet. 2024 Aug 26;17(1):19. doi: 10.1186/s13039-024-00689-x.
Chromoanagenesis is an umbrella term used to describe catastrophic "all at once" cellular events leading to the chaotic reconstruction of chromosomes. It is characterized by numerous rearrangements involving a small number of chromosomes/loci, copy number gains in combination with deletions, reconstruction of chromosomal fragments with improper order/orientation, and preserved heterozygosity in copy number neutral regions. Chromoanagesis is frequently described in association with cancer; however, it has also been described in the germline. The clinical features associated with constitutional chromoanagenesis are typically due to copy number changes and/or disruption of genes or regulatory regions.
We present an 8-year-old male patient with complex rearrangements of the Y chromosome including a ring Y chromosome, a derivative Y;21 chromosome, and a complex rearranged Y chromosome. These chromosomes were characterized by G-banded chromosome analysis, SNP microarray, interphase FISH, and metaphase FISH. The mechanism(s) by which these rearrangements occurred is unclear; however, it is evocative of chromoanagenesis.
This case is a novel example of suspected germline chromoanagenesis leading to large copy number changes that are well-tolerated, possibly because only the sex chromosomes are affected.
染色体混乱是一个概括性术语，用于描述导致染色体混乱重组的灾难性“一次性”细胞事件。其特征包括涉及少数染色体/基因座的大量重排、拷贝数增加与缺失并存、染色体片段以不正确的顺序/方向进行重组，以及拷贝数中性区域的杂合性得以保留。染色体混乱常与癌症相关；然而，它也在种系中被描述过。与先天性染色体混乱相关的临床特征通常归因于拷贝数变化和/或基因或调控区域的破坏。
我们报告一名8岁男性患者，其Y染色体存在复杂重排，包括一个环状Y染色体、一个衍生的Y;21染色体和一个复杂重排的Y染色体。通过G显带染色体分析、单核苷酸多态性微阵列、间期荧光原位杂交和中期荧光原位杂交对这些染色体进行了特征描述。这些重排发生的机制尚不清楚；然而，这让人联想到染色体混乱。
该病例是疑似种系染色体混乱导致大量拷贝数变化且耐受性良好的一个新例子，可能是因为仅性染色体受到影响。
