体质性染色体片段化融合:一名患者罕见染色体事件的描述。

Constitutional chromoanasynthesis: description of a rare chromosomal event in a patient.

作者信息

Plaisancié Julie, Kleinfinger Pascale, Cances Claude, Bazin Anne, Julia Sophie, Trost Detlef, Lohmann Laurence, Vigouroux Adeline

机构信息

Service de Génétique Médicale, Hôpital Purpan, CHU Toulouse, France.

Laboratoire Cerba, Département de Génétique Humaine, Saint-Ouen l'Aumône, France.

出版信息

Eur J Med Genet. 2014 Oct;57(10):567-70. doi: 10.1016/j.ejmg.2014.07.004. Epub 2014 Aug 13.

Abstract

Structural alterations in chromosomes are a frequent cause of cancers and congenital diseases. Recently, the phenomenon of chromosome crisis, consisting of a set of tens to hundreds of clustered genomic rearrangements, localized in one or a few chromosomes, was described in cancer cells under the term chromothripsis. Better knowledge and recognition of this catastrophic chromosome event has brought to light two distinct entities, chromothripsis and chromoanasynthesis. The complexity of these rearrangements and the original descriptions in tumor cells initially led to the thought that it was an acquired anomaly. In fact, a few patients have been reported with constitutional chromothripsis or chromoanasynthesis. Using microarray we identified a very complex chromosomal rearrangement in a patient who had a cytogenetically visible rearrangement of chromosome 18. The rearrangement contained more than 15 breakpoints localized on a single chromosome. Our patient displayed intellectual disability, behavioral troubles and craniofacial dysmorphism. Interestingly, the succession of duplications and triplications identified in our patient was not clustered on a single chromosomal region but spread over the entire chromosome 18. In the light of this new spectrum of chromosomal rearrangements, this report outlines the main features of these catastrophic events and discusses the underlying mechanism of the complex chromosomal rearrangement identified in our patient, which is strongly evocative of a chromoanasynthesis.

摘要

染色体结构改变是癌症和先天性疾病的常见原因。最近,在癌细胞中发现了一种名为染色体碎裂的现象,它由一组数十到数百个聚集的基因组重排组成,局限于一条或几条染色体上。对这种灾难性染色体事件的深入了解和认识揭示了两个不同的实体:染色体碎裂和染色体片段化合成。这些重排的复杂性以及最初在肿瘤细胞中的描述最初导致人们认为这是一种后天性异常。事实上,已经报道了一些患有先天性染色体碎裂或染色体片段化合成的患者。我们使用微阵列技术在一名染色体18发生细胞遗传学可见重排的患者中鉴定出一种非常复杂的染色体重排。这种重排包含15个以上位于单一染色体上的断点。我们的患者表现出智力残疾、行为问题和颅面畸形。有趣的是,在我们患者中鉴定出的重复和三倍体序列并非聚集在单一染色体区域,而是分布在整个18号染色体上。鉴于这种新的染色体重排谱,本报告概述了这些灾难性事件的主要特征,并讨论了在我们患者中鉴定出的复杂染色体重排的潜在机制,这强烈提示了染色体片段化合成。

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