A lethal phenotype associated with tissue plasminogen deficiency in humans

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• 作者：Hanan E. Shamseldin ; Abdulrahman Aldeeri ; Zainab Babay…
• 刊名：Human Genetics
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：135
• 期：10
• 页码：1209-1211
• 全文大小：1,591 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Human Genetics
  Molecular Medicine
  Internal Medicine
  Metabolic Diseases
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1203
• 卷排序：135

文摘

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.