Section of Genome Diagnostics, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.
Am J Med Genet A. 2012 Nov;158A(11):2888-93. doi: 10.1002/ajmg.a.35580. Epub 2012 Sep 17.
Complex chromosome rearrangements (CCRs) are rare genomic structural aberrations involving three or more breakpoints on two or more chromosomes. About one-third of all CCRs are familial. Transmittance of such a CCR results either in genomic imbalance due to abnormal segregation at meiosis I or is stably passed on to the next generation. Here we present a phenotypically normal mother with a CCR involving chromosomes 1, 3, and 5 that gave birth to a phenotypically abnormal son. The boy presented with hypotonia, mild facial dysmorphisms, and severe intellectual disability. Conventional karyotyping revealed the same apparently balanced CCR as in the mother. However, by use of array-comparative genome hybridization (array-CGH) and fluorescence in situ hybridization (FISH) we discovered that one of the derivative chromosomes in the patient contained a de novo rearrangement. It appears that during transmission of the CCR, an additional de novo deletion and duplication had arisen in one of the derivative chromosomes. We speculate that this was the result of the inverted duplication with a distal deletion mechanism. We also demonstrate the importance of high-resolution breakpoint analysis in CCRs and stress that genetic counseling of a familial CCR is not straightforward. To our knowledge, this would be the first description of this mechanism operating on a structurally abnormal chromosome.
复杂染色体重排（CCR）是一种罕见的基因组结构异常，涉及两个或多个染色体上的三个或更多断裂点。大约三分之一的 CCR 是家族性的。这种 CCR 的传递要么导致减数分裂 I 中异常分离导致基因组失衡，要么稳定地传递给下一代。在这里，我们介绍了一位表型正常的母亲，她携带涉及 1、3 和 5 号染色体的 CCR，生下了一个表型异常的儿子。这个男孩表现出张力减退、轻微的面部畸形和严重的智力残疾。常规核型分析显示与母亲相同的明显平衡 CCR。然而，通过使用阵列比较基因组杂交（array-CGH）和荧光原位杂交（FISH），我们发现患者的一个衍生染色体中存在一个新的重排。似乎在 CCR 的传递过程中，一个衍生染色体中的一个新的缺失和重复发生了。我们推测这是反向重复与远端缺失机制的结果。我们还证明了在 CCR 中进行高分辨率断点分析的重要性，并强调家族性 CCR 的遗传咨询并不简单。据我们所知，这将是第一个描述这种机制作用于结构异常染色体的描述。
