Rosenberg Carla, Knijnenburg Jeroen, Chauffaille Maria de Lourdes, Brunoni Decio, Catelani Ana Lucia, Sloos Willem, Szuhai Károly, Tanke Hans J
Laboratory of Cytochemistry and Cytometry, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
Hum Genet. 2005 Apr;116(5):390-4. doi: 10.1007/s00439-004-1248-x. Epub 2005 Feb 22.
Balanced complex chromosome rearrangements (CCR) are extremely rare in humans. They are usually ascertained either by abnormal phenotype or reproductive failure in carriers. These abnormalities are attributed to disruption of genes at the breakpoints, position effect or cryptic imbalances in the genome. However, little is known about possible imbalances at the junction points. We report here a patient with a CCR involving three chromosomes (2;10;11) and eight breakpoints. The patient presented with behavioural problems as the sole phenotypic abnormality. The rearrangement, which is apparently balanced in G-banding and multicolour FISH, was shown by genomic array analysis to include a deletion of 0.15-1.5 Mb associated with one of the breakpoints. To explain the formation of this rearrangement through the smallest possible number of breakage-and-reunion events, one has to assume that the breaks have not occurred simultaneously, but in a temporal order within the span of a single cell division. We demonstrate that array comparative genomic hybridisation (CGH) is a useful complementary tool to cytogenetic analysis for detecting and mapping cryptic imbalances associated with chromosome rearrangement.
平衡的复杂染色体重排（CCR）在人类中极为罕见。它们通常通过携带者的异常表型或生殖失败来确定。这些异常归因于断点处基因的破坏、位置效应或基因组中的隐匿性失衡。然而，关于连接点处可能存在的失衡情况却知之甚少。我们在此报告一名患有涉及三条染色体（2号、10号和11号）及八个断点的CCR患者。该患者仅表现出行为问题这一唯一的表型异常。在G显带和多色荧光原位杂交中看似平衡的重排，经基因组阵列分析显示其中一个断点处存在0.15 - 1.5 Mb的缺失。为了通过尽可能少的断裂和重聚事件来解释这种重排的形成，必须假定这些断裂并非同时发生，而是在单个细胞分裂的时间段内按时间顺序发生。我们证明，阵列比较基因组杂交（CGH）是细胞遗传学分析的一种有用的补充工具，可用于检测和定位与染色体重排相关的隐匿性失衡。
