Rowe L R, Lee J-Y, Rector L, Kaminsky E B, Brothman A R, Martin C L, South S T
J Med Genet. 2009 Oct;46(10):694-702. doi: 10.1136/jmg.2008.065052. Epub 2009 Mar 16.
Chromosomal rearrangements resulting in an interstitial inverted duplication with concomitant terminal deletion were first described for the short arm of chromosome 8 in 1976. Since then, this type of alteration has been identified and characterised for most chromosome arms. Three mechanisms are commonly proposed to explain the origin of this type of rearrangement. All three mechanisms involve formation of a dicentric chromosome that then breaks in a subsequent meiotic division to produce a monocentric duplicated and deleted chromosome. However, the events leading to the formation of the dicentric chromosome differ between the mechanisms. In one mechanism, either parent carries a paracentric inversion. This results in formation of a loop during meiotic pairing with a recombination event occurring in the loop. In the second mechanism, inverted low copy repeats in the same chromosome arm allow partial folding of one homologue onto itself with a recombination event between the inverted repeats. The third mechanism involves a pre-meiotic double-strand break with subsequent fusion, or U-type exchange, between the sister chromatids. The first two mechanisms require a single copy region to exist between the duplicated and deleted regions on the derivative chromosome, and therefore high resolution analysis of the rearrangement can be used to distinguish between these mechanisms.
Using G-banded chromosome analysis, fluorescence in situ hybridisation (FISH) and array comparative genomic hybridisation (CGH), we describe 17 new cases of inverted duplication with terminal deletion of 2q, 4p, 5p, 6q, 8p, 9p, 10q, 13q, 15q, 18p, 18q, and 22q.
These new cases, combined with previously described cases, demonstrate that U-type exchange is the most frequent mechanism for this rearrangement and can be observed on most, or perhaps all, chromosome arms.
1976年首次报道了导致中间倒位重复并伴有末端缺失的染色体重排，涉及8号染色体短臂。从那时起，这种类型的改变已在大多数染色体臂上得到鉴定和表征。通常提出三种机制来解释这种重排的起源。所有这三种机制都涉及双着丝粒染色体的形成，然后在随后的减数分裂中断裂，产生单着丝粒重复和缺失的染色体。然而，导致双着丝粒染色体形成的事件在这些机制之间有所不同。在一种机制中，父母任何一方携带臂内倒位。这导致减数分裂配对期间形成一个环，环内发生重组事件。在第二种机制中，同一染色体臂上的反向低拷贝重复序列允许一个同源染色体部分折叠到自身上，在反向重复序列之间发生重组事件。第三种机制涉及减数分裂前的双链断裂，随后姐妹染色单体之间发生融合或U型交换。前两种机制要求在衍生染色体上的重复和缺失区域之间存在一个单拷贝区域，因此对重排进行高分辨率分析可用于区分这些机制。
使用G带染色体分析、荧光原位杂交（FISH）和阵列比较基因组杂交（CGH），我们描述了17例新的2号染色体长臂、4号染色体短臂、5号染色体短臂、6号染色体长臂、8号染色体短臂、9号染色体短臂、10号染色体长臂、13号染色体长臂、15号染色体长臂、18号染色体短臂、18号染色体长臂和22号染色体长臂倒位重复并伴有末端缺失的病例。
这些新病例与先前描述的病例相结合，表明U型交换是这种重排最常见的机制，并且可以在大多数或可能所有染色体臂上观察到。
