A novel Asp344Val substitution in the fibrinogen gamma chain (fibrinogen Caen) causes dysfibrinogenemia associated with thrombosis.
A 5-year-old boy was hospitalized for acute appendicitis. Routine preoperative hemostasis screening resulted in a diagnosis of dysfibrinogenemia. Fifteen days after the operation the patient was re-hospitalized for deep vein thrombosis. Genetic analysis of the fibrinogen genes revealed a novel missense mutation in exon 8 of fibrinogen gamma-chain gene (FGG): c.1031A>T, p.Asp344Val (p.Asp318Val in the mature chain) in heterozygosity. Interestingly, this same residue in the fibrinogen gamma chain was previously found to be mutated to a glycine (fibrinogen Giessen IV) in another young dysfibrinogenemia patient with thrombosis. The side chain of Asp344 (or Asp318) in the gamma chain is directly involved in binding to calcium. Abnormal polymerization of fibrin in fibrinogen Giessen IV and in the novel fibrinogen Caen described here could lead to the formation of abnormal clots leading to thrombosis, in addition to abnormal thrombin binding and decreased fibrinolysis.
Robert-Ebadi
Helia
H
Division of Angiology and Haemostasis, University Hospital, Geneva, Switzerland.
Le Querrec
Agnès
A
de Moerloose
Philippe
P
Gandon-Laloum
Sylvie
S
Borel Derlon
Annie
A
Neerman-Arbez
Marguerite
M
D000347:Afibrinogenemia / Q000209:etiology / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002675:Child, Preschool; D005340:Fibrinogen / Q000235:genetics*; D015241:Fibrinogens, Abnormal / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D020246:Venous Thrombosis / Q000150:complications / Q000235:genetics*
D015241:Fibrinogens, Abnormal; C027539:fibrinopeptides gamma; D005340:Fibrinogen