Shimokawa Osamu, Kurosawa Kenji, Ida Tomoko, Harada Naoki, Kondoh Tatsuro, Miyake Noriko, Yoshiura Kohichiro, Kishino Tatsuya, Ohta Tohru, Niikawa Norio, Matsumoto Naomichi
Kyusyu Medical Science Nagasaki Laboratory, Nagasaki, Japan.
Am J Med Genet A. 2004 Jul 15;128A(2):133-7. doi: 10.1002/ajmg.a.30063.
We analyzed five patients with inverted duplication deletion of 8p [inv dup del(8p)] using fluorescence in situ hybridization (FISH) and short tandem repeat polymorphism (STRP) analysis. In all patients, inv dup del(8p) consisted of a deleted distal segment, an intact in-between segment, and a duplicated proximal segment. In all of them, the proximal breakpoint of the deletion and one of the breakpoints of the duplication were identical, each located at one of the two olfactory receptor gene clusters at 8p23. FISH analysis showed all their mothers to be heterozygous carriers of an 8p23 inversion [inv(8)(p23)]. STRP analysis indicated that the deletions occurred in maternally derived chromosomes. The duplicated segments had two copies of maternal, either heterozygous or homozygous alleles. These findings support and reinforce those in 16 patients with inv dup del(8p) and their parents by Floridia et al. [1996: Am J Hum Genet 58:785-796] and subsequent additional studies of 10 of them by Giglio et al. [2001: Am J Hum Genet 68:874-883]. Based on these findings, we propose a model for the inv dup del(8p) formation. The inverted segment and its normal counterpart in inv(8)(p23) heterozygous carrier mothers form a loop at the pachytene period of meiosis I. Inv dup del(8p) with heterozygous duplication is formed through at least one meiotic recombination within the loop. Inv dup del(8p) with the homozygous duplication arises through two meiotic recombinations on the inv(8)(p23) chromosome (one within the loop and the other between the loop and centromere). Subsequent rescue by eliminating a part of the duplicated segment and a centromere enables formation of viable inv dup del(8p). The frequency of the inv(8)(p23) allele is 39% in a normal Japanese population, comparable to 26% in Europeans Giglio et al. [2001: Am J Hum Genet 68:874-883]. The proposed mechanism of formation of inv dup del(8p) requires two independent events (a recombination within the loop and subsequent rescue), which may explain its rarity.
我们使用荧光原位杂交（FISH）和短串联重复序列多态性（STRP）分析，对5例8号染色体短臂反向重复缺失[inv dup del(8p)]患者进行了分析。在所有患者中，inv dup del(8p)均由一个缺失的远端片段、一个完整的中间片段和一个重复的近端片段组成。在所有患者中，缺失的近端断点和重复的断点之一是相同的，均位于8p23的两个嗅觉受体基因簇之一处。FISH分析显示，他们的母亲均为8p23倒位[inv(8)(p23)]的杂合携带者。STRP分析表明，缺失发生在母源染色体上。重复片段有两份母源等位基因拷贝，要么是杂合的，要么是纯合的。这些发现支持并强化了Floridia等人[1996年：《美国人类遗传学杂志》58:785 - 796]对16例inv dup del(8p)患者及其父母的研究结果，以及随后Giglio等人[2001年：《美国人类遗传学杂志》68:874 - 883]对其中10例患者的进一步研究结果。基于这些发现，我们提出了一个inv dup del(8p)形成的模型。inv(8)(p23)杂合携带者母亲中的倒位片段及其正常对应片段在减数分裂I的粗线期形成一个环。具有杂合重复的inv dup del(8p)是通过环内至少一次减数分裂重组形成的。具有纯合重复的inv dup del(8p)是通过inv(8)(p23)染色体上的两次减数分裂重组产生的（一次在环内，另一次在环与着丝粒之间）。随后通过消除部分重复片段和一个着丝粒进行挽救，从而形成可行的inv dup del(8p)。在正常日本人群中，inv(8)(p23)等位基因的频率为39%，与欧洲人群中的26%相当[Giglio等人，2001年：《美国人类遗传学杂志》68:874 - 883]。所提出的inv dup del(8p)形成机制需要两个独立事件（环内重组和随后的挽救），这可能解释了它的罕见性。
