| Autor: |
Bayston TA; Imperial College School of Medicine, London, UK., Tripodi A, Mannucci PM, Thompson E, Ireland H, Fitches AC, Hananeia L, Olds RJ, Lane DA |
| Jazyk: |
angličtina |
| Zdroj: |
Blood [Blood] 1999 Jun 15; Vol. 93 (12), pp. 4242-7. |
| Abstrakt: |
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: |
MEDLINE |
| Externí odkaz: |
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