Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome
Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome
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DOI：
10.1038/ejhg.2013.45
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发表时间：
2013-11-01
影响因子：
5.2
通讯作者：
Soejima, Hidenobu
中科院分区：
文献类型：
--
作者：
Higashimoto, Ken;Maeda, Toshiyuki;Soejima, Hidenobu
珀尔曼综合征是一种罕见的常染色体隐性遗传性过度生长障碍。最近，已有病例报道了Dis3l2基因外显子9的缺失和其他突变，但这种缺失背后的机制仍不清楚。我们报告一例日本Perlman综合征患者的Dis3l2基因外显子9纯合缺失。我们确定了缺失连接，并暗示两个Line-1(L1)元件之间的非等位同源重组(Nahr)是导致该基因缺失的机制。此外，父本突变等位基因和母本突变等位基因之间的缺失连接也不同，这表明在每个亲本的祖先中都发生了两个独立的Nahr事件。这些数据表明，外显子9附近的区域可能是L1介导的Nahr的一个热点。
Perlman syndrome is a rare, autosomal recessive overgrowth disorder. Recently, the deletion of exon 9 and other mutations of the DIS3L2 gene have been reported in patients; however, the mechanism behind this deletion is still unknown. We report the homozygous deletion of exon 9 of DIS3L2 in a Japanese patient with Perlman syndrome. We identified the deletion junction, and implicate a non-allelic homologous recombination (NAHR) between two LINE-1 (L1) elements as the causative mechanism. Furthermore, the deletion junctions were different between the paternal and maternal mutant alleles, suggesting the occurrence of two independent NAHR events in the ancestors of each parent. The data suggest that the region around exon 9 might be a hot spot of L1-mediated NAHR.