Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
Eur J Hum Genet. 2013 Nov;21(11):1316-9. doi: 10.1038/ejhg.2013.45. Epub 2013 Mar 13.
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.
佩尔曼综合征是一种罕见的常染色体隐性过度生长疾病。最近，在患者中已报道了 DIS3L2 基因的外显子 9 缺失和其他突变；然而，这种缺失的机制尚不清楚。我们报道了一例日本佩尔曼综合征患者 DIS3L2 基因第 9 外显子的纯合缺失。我们确定了缺失的连接点，并暗示两个 LINE-1（L1）元件之间的非等位基因同源重组（NAHR）是致病机制。此外，父本和母本突变等位基因的缺失连接点不同，提示在每个亲本的祖先中发生了两次独立的 NAHR 事件。这些数据表明，exon 9 周围的区域可能是 L1 介导的 NAHR 的热点。
