A familial inverted duplication/deletion of 2p25.1-25.3 provides new clues on the genesis of inverted duplications
A familial inverted duplication/deletion of 2p25.1-25.3 provides new clues on the genesis of inverted duplications
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DOI：
10.1038/ejhg.2008.160
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发表时间：
2009-02-01
影响因子：
5.2
通讯作者：
Zuffardi, Orsetta
中科院分区：
文献类型：
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作者：
Bonaglia, Maria Clara;Giorda, Roberto;Zuffardi, Orsetta
我们研究了一个家庭，在两个孩子和他们的父亲中，2p25.3-p25.1相同的10mb反向重复分离，都表现出三体表型。由于FISH分析显示重复是反向的，我们怀疑根据经典的反向重排类型，也存在连续的末端缺失。尽管使用2p和2q亚端粒探针的FISH结果正常，但100 kb分辨率的array-C\GH （aCGH）显示，除了重复外，还存在273 kb的缺失。通过高分辨率aCGH分析（类似于20 kb），进一步怀疑在删除和复制区域之间存在单拷贝区域，尽管只检测到一个具有正常对数比的信息点。通过实时PCR和断点克隆重新定义了重排的精确结构，证明在删除区和重复区之间存在2680 bp的单拷贝序列，并且涉及一个简单的重复，具有形成非b DNA结构的潜力。重排不是通过片段复制或短倒重复介导的，双链断裂可能通过非同源末端连接或微同源介导的链内修复来修复。这些数据强调了这样一个事实，即与反向重复相关的伴随缺失很可能比经典细胞遗传学方法单独能够证明的更频繁。讨论了三体和末端2p缺失的表型效应。
We studied a family in which the same 10 Mb inverted duplication of 2p25.3-p25.1 segregates in two children and their father, all showing a trisomy phenotype. As FISH analysis demonstrated that the duplication was inverted, we suspected that a contiguous terminal deletion was also present, according to the classical inv dup del type of rearrangements. Although FISH with 2p and 2q subtelomeric probes gave normal results, 100 kb resolution array-C\GH (aCGH) showed that, beside the duplication, a 273 kb deletion was also present. The presence of a single-copy region between the deleted and duplicated regions was further suspected through high-resolution aCGH analysis (similar to 20 kb), although only one informative spot having a normal log ratio was detected. The precise structure of the rearrangement was re-defined by real-time PCR and breakpoint cloning, demonstrating the presence of a 2680 bp single-copy sequence between deleted and duplicated regions and the involvement of a simple repeat with the potential for forming a non-B DNA structure. The rearrangement was not mediated by segmental duplications or short inverted repeats, and the double-strand break might have been repaired by non-homologous end joining or microhomology-mediated intrastrand repair. These data highlight the fact that concomitant deletions associated with inverted duplications are very likely to be more frequent than classical cytogenetic methods alone have been able to demonstrate. The phenotypic effects of the trisomy and of the terminal 2p deletion are discussed.