The molecular basis of antithrombin deficiency in Belgian and Dutch families
(1998) Thrombosis and Haemostasis : international journal for vascular biology and medicine — Vol. 80, n° 3, p. 376-381 (1998)
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- Abstract
- The molecular basis of hereditary antithrombin (AT) deficiency has been investigated in ten Belgian and three Dutch unrelated kindreds. Eleven of these families had a quantitative or type I AT deficiency. with a history of major venous thromboembolic events in different affected members. In the other two families a qualitative or type I AT deficiency was occasionally diagnosed. DNA studies of the AT gene were performed, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis, followed by direct sequencing of the seven exons and intron-exon junction regions. Six novel point mutations were identified: four missense, one nonsense mutation and a single nucleotide deletion near the reactive site, causing a frameshift with premature translation termination. In two kindreds the underlying genetic defect was caused by a whole gene deletion. known as a rare cause of AT deficiency. In these cases, Southern blot and polymorphism analysis of different parts of the AT gene proved useful for diagnosis. In another kindred a partial gene deletion spanning 698 basepairs could precisely be determined to a part of intron 3B and exon 4. In two type I and in both type II AT deficient families a previously reported mutation was identified. In all cases, the affected individuals were heterozygous for the genetic defect.
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Jochmans, K., Lissens, W., Seneca, S., Capel, P., Chatelain, B., Meeus, P., Osselaer, J.-C., Peerlinck, K., Seghers, J., Slacmeulder, M., Stibbe, J., van de Loo, J., Vermylen, J., Liebaers, I., & De Waele, M. (1998). The molecular basis of antithrombin deficiency in Belgian and Dutch families. Thrombosis and Haemostasis : international journal for vascular biology and medicine, 80(3), 376-381. https://hdl.handle.net/2078.5/85324 (Original work published 1998)