Creation of an additional glycosylation site as a mechanism for type I antithrombin deficiency.

摘要: We report the identification of a new mutation resulting in type I antithrombin (AT) deficiency and mechanism by which arose. The single base substitution G to A at nucleotide 2709 was identified proband with family history venous thrombosis. results 82 Ser Asn, creating glycosylation site. Expression studies were then carried out, confirm Asn-linked occurred this consensus site that resulted AT deficient phenotype. Cell-free translations using rabbit reticulocyte lysate presence microsomes demonstrated Asn variant post-translationally processed efficiently. protein higher molecular weight than normal AT. consistent addition fifth glycan chain. Incubation translation product endoglycosidase H, confirmed had from additional carbohydrate. COS-7 cells intracellular accumulation, low level secretion into culture supernatant, deficiency. an extra carbohydrate side chain residue may block post-translational folding. trapping intracellulary.