Abstract：
Alu elements are short, interspersed elements located throughout the genome, playing a role in human diversity, and occasionally causing genetic diseases. Here, we report a novel Alu insertion causing Mowat-Wilson syndrome, a rare neurodevelopmental disorder, in an 8-year-old boy displaying the typical clinical features for Mowat-Wilson syndrome. The variant was not initially detected in genome sequencing data, but through deep phenotyping, which pointed to only one plausible candidate gene, manual inspection of genome sequencing alignment data enabled us to identify a de novo heterozygous Alu insertion in exon 8 of the ZEB2 gene. Nanopore long-read sequencing confirmed the Alu insertion, leading to the formation of a premature stop codon and likely haploinsufficiency of ZEB2. This underscores the importance of deep phenotyping and mobile element insertion analysis in uncovering genetic causes of monogenic disorders as these elements might be overlooked in standard next-generation sequencing protocols.
摘要：
Alu元素很短，散布在整个基因组中的元件，在人类多样性中发挥作用，偶尔会引起遗传疾病。这里,我们报道了一种新的Alu插入导致Mowat-Wilson综合征，一种罕见的神经发育障碍,一名8岁男孩表现出Mowat-Wilson综合征的典型临床特征。最初在基因组测序数据中未检测到该变异，但是通过深度表型，只指出了一个似是而非的候选基因,手动检查基因组测序比对数据使我们能够鉴定ZEB2基因外显子8中的从头杂合Alu插入.纳米孔长读数测序证实了Alu的插入，导致过早终止密码子的形成和可能的ZEB2单倍体不足。这强调了深度表型和移动元素插入分析在发现单基因疾病的遗传原因中的重要性，因为这些元素可能在标准的下一代测序方案中被忽略。
