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Molecular bases of antithrombin deficiency: twenty‐two novel mutations in the antithrombin gene
Author(s) -
Picard Véronique,
NowakGöttl Ulrike,
BironAndreani Christine,
Fouassier Marc,
Frere Corinne,
GoualtHeilman Michèle,
de Maistre Emmanuel,
Regina Sandra,
Rugeri Lucia,
Ternisien Catherine,
Trichet Catherine,
Vergnes Christine,
Aiach Martine,
AlhencGelas Martine
Publication year - 2006
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9425
Subject(s) - antithrombin , biology , gene , antithrombin iii deficiency , genetics , mutation , antithrombins , biochemistry , heparin
Antithrombin (AT) is a major physiological inhibitor of hemostasis. We report 22 novel antithrombin gene ( SERPINC1 ) mutations associated with antithrombin deficiency in 17 French and five German families. They were all present at the heterozygous state. Nine missense mutations accounted for type I deficiency, defined by equally low antithrombin activity and antigen level. Most of them (7/9) affected highly conserved serpin residues and were associated with venous thrombosis occuring at a young age (before age 32). One splice site, one nonsense mutation, three small deletions and one insertion were also identified as a cause for type I antithrombin deficiency. Seven other missense mutations were identified in type II or unclassified AT deficiency; g.5270C>T (p.T147I, T115I) and g.5281A>T (p.I151F, I119F) change residues in the heparin binding region, g.13267C>G (p.P439A, P407A) and g.13271T>C (p.F440S, F408S) affect amino acids in the pleiotropic region, g.2372G>A (p.G25D, G‐8D) changes a signal peptide amino acid, g.2456G>C (p.C53S, C21S) affects one of the three disulfide bonds of the protein, and g.7585A>T (p.M347K, M315K) changes a nonconserved residue on strand 2C. © 2006 Wiley‐Liss, Inc.