The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes
The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes
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DOI：
10.1136/jmg.2004.024141
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发表时间：
2005-01-01
影响因子：
4
通讯作者：
Carter, NP
中科院分区：
文献类型：
--
作者：
Gribble, SM;Prigmore, E;Carter, NP
目的：描述系统分析表现为异常表型的患者的先天性从头明显平衡易位，分析结构染色体重排，绘制易位断裂点，并报告可检测的基因组不平衡。利用阵列CGH技术筛选染色体组不平衡，利用阵列涂绘技术快速定位染色体断裂点。这两种方法有助于快速分析易位断裂点和筛查隐性染色体不平衡。重排的断点，进一步完善（跨越克隆的水平）使用荧光原位杂交在appropriate.Results：意想不到的额外的复杂性或基因组不平衡的10例研究中发现6。根据染色体组型重排的一般性质，患者可分组如下：（A）三例复杂的多重重排，包括在一个或两个断点处或附近的缺失、倒位和插入;（B）三例易位似乎平衡，但微阵列分析鉴定出与易位无关的染色体上先前未识别的不平衡;（C）4例易位断裂点在所用分辨率下表现为简单和平衡。这种高水平的意想不到的重排复杂性，如果在进一步的患者研究中得到普遍证实，将对目前这种类型的诊断研究产生影响，并为更广泛地采用微阵列分析或其他高分辨率基因组-染色体不平衡和重排的筛查
Objective: To describe the systematic analysis of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes, characterise the structural chromosome rearrangements, map the translocation breakpoints, and report detectable genomic imbalances.Methods: DNA microarrays were used with a resolution of 1 Mb for the detailed genome- wide analysis of the patients. Array CGH was used to screen for genomic imbalance and array painting to map chromosome breakpoints rapidly. These two methods facilitate rapid analysis of translocation breakpoints and screening for cryptic chromosome imbalance. Breakpoints of rearrangements were further refined ( to the level of spanning clones) using fluorescence in situ hybridisation where appropriate.Results: Unexpected additional complexity or genome imbalance was found in six of 10 patients studied. The patients could be grouped according to the general nature of the karyotype rearrangement as follows: ( A) three cases with complex multiple rearrangements including deletions, inversions, and insertions at or near one or both breakpoints; ( B) three cases in which, while the translocations appeared to be balanced, microarray analysis identified previously unrecognised imbalance on chromosomes unrelated to the translocation; ( C) four cases in which the translocation breakpoints appeared simple and balanced at the resolution used.Conclusions: This high level of unexpected rearrangement complexity, if generally confirmed in the study of further patients, will have an impact on current diagnostic investigations of this type and provides an argument for the more widespread adoption of microarray analysis or other high resolution genome- wide screens for chromosome imbalance and rearrangement.