Ring chromosome formation as a novel escape mechanism in patients with inverted duplication and terminal deletion
Ring chromosome formation as a novel escape mechanism in patients with inverted duplication and terminal deletion
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DOI：
10.1038/sj.ejhg.5201807
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发表时间：
2007-05-01
影响因子：
5.2
通讯作者：
Szuhai, Karoly
中科院分区：
文献类型：
--
作者：
Knijnenburg, Jeroen;van Haeringen, Arie;Szuhai, Karoly
环状染色体是罕见的细胞遗传学发现，并在表型水平与智力低下和先天性异常。环状染色体综合征的特异性特征通常与相应染色体的末端缺失特征重叠。在这里，我们报告了一例环状14号染色体的病例，该染色体通过常规细胞遗传学鉴定，并通过使用大插入克隆和寡聚阵列比较基因组杂交（阵列CGH）、荧光原位杂交（FISH）和多重连接依赖性探针扩增（MLPA）显示具有末端缺失和额外的反向重复与三重。环状染色体中的反向重复与末端缺失的组合对于所描述的14号染色体综合征特别感兴趣。所提出的研究结果可能解释部分重叠的临床特征中描述的末端缺失，重复和环状染色体14的情况下，这些重排可以很容易地被忽视时，执行GTG显带。此外，我们认为，环状染色体的形成可以作为一种替代的染色体拯救旁边的端粒愈合和捕获，特别是对近端着丝粒染色体。据我们所知，这是第一次在一个环形染色体末端缺失的反向重复被确定和特点，使用高分辨率分子核型分析。通过阵列CGH对环状染色体进行系统评价可能特别有助于区分重复/缺失与仅缺失的病例。
Ring chromosomes are rare cytogenetic findings and are associated at phenotypic level with mental retardation and congenital abnormalities. Features specific for ring chromosome syndromes often overlap with the features of terminal deletions for the corresponding chromosomes. Here, we report a case of a ring chromosome 14 which was identified by conventional cytogenetics and shown to have a terminal deletion and an additional inverted duplication with a triplication by using large insert clone and oligo array-comparative genomic hybridization (array-CGH), fluorescence in situ hybridization ( FISH) and multiplex ligation-dependent probe amplification ( MLPA). The combination of an inverted duplication with a terminal deletion in a ring chromosome is of special interest for the described syndromes of chromosome 14. The presented findings might explain partly overlapping clinical features described in terminal deletion, duplication and ring chromosome 14 cases, as these rearrangements can be easily overlooked when performing GTG-banding only. Furthermore, we suggest that ring chromosome formation can act as an alternative chromosome rescue next to telomere healing and capture, particularly for acrocentric chromosomes. To our knowledge, this is the first time an inverted duplication with a terminal deletion in a ring chromosome is identified and characterized using high-resolution molecular karyotyping. Systematic evaluation of ring chromosomes by array-CGH might be especially useful in distinguishing cases with a duplication/deletion from those with a deletion only.