Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Department of Internal Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Hum Genet. 2016 Oct;135(10):1209-11. doi: 10.1007/s00439-016-1711-5. Epub 2016 Jul 14.
The role of plasminogen in preventing thrombosis requires activation by tissue plasminogen activator (t-PA) encoded by PLAT. While case-control associations have been pursued for common variants in PLAT, no disease-causing mutations have been reported. We describe a consanguineous family with two children who died shortly after birth due to complications related to severe hydranencephaly and diaphragmatic hernia. A combined exome/autozygome analysis was carried out with informed consent. We identified a homozygous null mutation in PLAT that abrogated t-PA level in patient cells. This is the first reported human knockout mutation of PLAT. The apparent association with hydranencephaly, diaphragmatic hernia and postnatal lethality requires further validation.
纤溶酶原在预防血栓形成中的作用需要组织型纤溶酶原激活物（t-PA）的激活，而 t-PA 由 PLAT 编码。虽然已经针对 PLAT 中的常见变体进行了病例对照关联研究，但尚未报道致病突变。我们描述了一个有血缘关系的家庭，有两个孩子在出生后不久因严重的无脑畸形和横膈疝相关并发症而死亡。在知情同意的情况下，进行了外显子组/自交系分析。我们在 PLAT 中发现了一个纯合性缺失突变，导致患者细胞中的 t-PA 水平降低。这是首次报道的人类 PLAT 基因敲除突变。与无脑畸形、横膈疝和出生后致死性的明显关联需要进一步验证。
