Schlade-Bartusiak Kamilla, Tucker Tracy, Safavi Holly, Livingston Janet, van Allen Margot I, Eydoux Patrice, Armstrong Linlea
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
Eur J Med Genet. 2013 May;56(5):229-35. doi: 10.1016/j.ejmg.2013.01.013. Epub 2013 Feb 14.
Mosaicism with two cell lines having different rearrangements of the same chromosome is rare. Only a few cases of mosaicism have been described in association with chromosomal inverted duplication deletion (inv dup del) rearrangements. A well-established mechanism of formation of inv dup del rearrangements involves a dicentric intermediate, which undergoes breakage during cell division, generating cells with either an inv dup del or a simple deletion. A patient with developmental delay and dysmorphic features was found to carry two cell lines with rearrangements of 9p: an inv dup del 9p and a terminal deletion 9p. Microarray and FISH analysis showed that these cell lines do not constitute the reciprocal products of a single dicentric breakage event. We propose that independent post-zygotic breaks of a dicentric chromosome as a likely mechanism leading to the generation of the observed cell lines. The post-zygotic origin of the inv dup del rearrangements and the associated mosaicism can be a more frequent phenomenon than currently appreciated. Therefore, genotype-phenotype correlations in the inv dup del rearrangements need to take into account the possible presence of other abnormal cell lines during early development.
具有两条细胞系且同一染色体存在不同重排的嵌合体现象较为罕见。仅有少数嵌合体病例与染色体倒位重复缺失(inv dup del)重排相关。一种已明确的inv dup del重排形成机制涉及一个双着丝粒中间体,其在细胞分裂过程中发生断裂,产生具有inv dup del或简单缺失的细胞。一名患有发育迟缓及畸形特征的患者被发现携带两条9号染色体发生重排的细胞系:一条inv dup del 9p和一条9p末端缺失。微阵列和荧光原位杂交分析表明,这些细胞系并非单个双着丝粒断裂事件的相互产物。我们提出,双着丝粒染色体的独立合子后断裂是导致观察到的细胞系产生的一种可能机制。inv dup del重排及相关嵌合体的合子后起源可能是一种比目前所认识到的更为常见的现象。因此,在inv dup del重排中进行基因型 - 表型相关性分析时,需要考虑早期发育过程中可能存在的其他异常细胞系。