A lethal phenotype associated with tissue plasminogen deficiency in humans

Shamseldin, Hanan; Aldeeri, Abdulrahman; Babay, Zainab; Alsultan, Abdulrahman; Hashem, Mais; Alkuraya, Fowzan
October 2016
Human Genetics;Oct2016, Vol. 135 Issue 10, p1209
Academic Journal
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.


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