Inherited abnormalities of fibrinogen: 10-year clinical experience of an Italian group.
Inherited abnormalities of fibrinogen present a high variability in penetrance and expressivity, and clinical manifestations vary from severe bleeding or thrombosis to asymptomatic This variability makes clinical and genetic counseling more difficult. We report the experience of a clinical group working in specialist centers in Southern Italy on a series of consecutive patients presenting with congenital abnormalities of fibrinogen. Over 10 years, 18 patients were diagnosed to carry a congenital abnormality of fibrinogen. These patients and 26 first-degree relatives were investigated in-depth to fully characterize the nature of their abnormal fibrinogen levels. A gene mutation was identified in 15 patients (four afibrinogenemic patients, three hypofibrinogenemic patients, and eight dysfibrinogenemic patients). A new mutation was found in four of them: Aalpha Arg159Stop in one afibrinogenemic patient, Aalpha Arg104Cys in two hypofibrinogenemic patients, and Aalpha Pro270Thr in one dysfibrinogenemic patient. While all afibrinogenemic patients had clinically important bleeding, participants presenting with hypofibrinogenemia remained asymptomatic. In the presence of the synthesis of an abnormal molecule, the clinical phenotype was not strictly related to plasma fibrinogen levels but was associated with the molecular defect, most carriers remaining asymptomatic. Personal and family histories of bleeding and thrombosis are important for the clinical management of patients presenting with congenital abnormalities of fibrinogen. Biochemical and genetic investigations may be a useful guide for decision-making, providing additional steps in the assessment of the risk of patients presenting with low levels of a normal molecule (hypofibrinogenemia and afibrinogenemia) and with an abnormal molecule (dysfibrinogenemia), respectively.
Santacroce
Rosa
R
Genetica Medica, Dipartimento di Scienze Biomediche, Università di Foggia, Italy.
Cappucci
Filomena
F
Pisanelli
Daniela
D
Perricone
Fabio
F
Papa
Maria Luisa
ML
Santoro
Rita
R
Grandone
Elvira
E
Margaglione
Maurizio
M
D000293:Adolescent; D000328:Adult; D000347:Afibrinogenemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D019943:Amino Acid Substitution; D025861:Blood Coagulation Disorders, Inherited / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D006801:Humans; D007223:Infant; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017354:Point Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D005340:Fibrinogen