| Autor: |
T A, Bayston, A, Tripodi, P M, Mannucci, E, Thompson, H, Ireland, A C, Fitches, L, Hananeia, R J, Olds, D A, Lane |
| Rok vydání: |
1999 |
| Předmět: |
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| Zdroj: |
Blood. 93(12) |
| ISSN: |
0006-4971 |
| Popis: |
We have investigated the basis of antithrombin deficiency in an asymptomatic individual (and family) with borderline levels (approximately 70% antigen and activity) of antithrombin. Direct sequencing of amplified DNA showed a mutation in codon 135, AAC to ACC, predicting a heterozygous Asn135Thr substitution. This substitution alters the predicted consensus sequence for glycosylation, Asn-X-Ser, adjacent to the heparin interaction site of antithrombin. The antithrombin isolated from plasma of the proband by heparin-Sepharose chromatography contained amounts of beta antithrombin (the very high affinity fraction) greatly increased (approximately 20% to 30% of total) above the trace levels found in normals. Expression of the residue 135 variant in both a cell-free system and COS-7 cells confirmed altered glycosylation arising as a consequence of the mutation. Wild-type and variant protein were translated and exported from COS-7 cells with apparently equal efficiency, in contrast to the reduced level of variant observed in plasma of the affected individual. This case represents a novel cause of antithrombin deficiency, removal of glycosylation concensus sequence, and highlights the potentially important role of beta antithrombin in regulating coagulation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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