Severe bleeding in a woman heterozygous for the fibrinogen gammaR275C mutation.
The dysfibrinogen gammaR275C can be a clinically silent mutation, with only two out of 17 cases in the literature reporting a hemorrhagic presentation and four cases reporting a thrombotic presentation. We describe here a particularly severe presentation in 54-year-old female patient who required a hysterectomy at 47 years of age due to heavy menstrual bleeding. Coagulation studies revealed a prolonged prothrombin time and thrombin time, a normal fibrinogen antigen level, and a low fibrinogen activity level. Molecular analysis of the patient's DNA revealed a gamma chain gene mutation resulting in an amino acid substitution at residue 275 (gammaR275C). Protein sequencing of the fibrinogen gamma chain confirmed this mutation, which was named Fibrinogen Portland I. This case demonstrates that the gammaR275C mutation can lead to a severe hemorrhagic phenotype.
Rein
Chantelle M
CM
Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, USA.
Anderson
Brian L
BL
Ballard
Morgan M
MM
Domes
Christopher M
CM
Johnston
Joshua M
JM
Madsen
Russell Jared
RJ
Wolper
Kathryn K M
KK
Terker
Andrew S
AS
Strother
John M
JM
Deloughery
Thomas G
TG
Farrell
David H
DH
D019943:Amino Acid Substitution; D001780:Blood Coagulation Tests; D005260:Female; D015241:Fibrinogens, Abnormal / Q000235:genetics* / Q000302:isolation & purification; D006579:Heterozygote; D006801:Humans; D008595:Menorrhagia / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense; D010641:Phenotype
D015241:Fibrinogens, Abnormal
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