PB0222 - A novel c.952G>T mutation in the FGG gene exon 8 causing Hypodysfibrinogenemia

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

AC

Aniello Casoria, MD

Resident
Federico II University of Naples
Naples, Campania, Italy

Co-Author(s)

CM

Ciro Miele

Resident
UOC Laboratory Medicine of Hematology and Hemostasis; Federico II University, Naples, Italy
Naples, Campania, Italy
FC

Filomena Capasso

Dr
UOC Laboratory Medicine of Hematology and Hemostasis; Federico II University, Naples, Italy
Naples, Campania, Italy
RM

Rosaria Mormile

Dr
Haematology, Department of Translational and precision Medicine, Sapienza University, Rome, Italy
Rome, Lazio, Italy
LB

Luigi Bisceglia

Professor
Division of medical Genetics IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
San Giovanni Rotondo, Puglia, Italy
GV

Gennaro Vecchione

Dr
Division of medical Genetics IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
San Giovanni Rotondo, Puglia, Italy
FC

Fedinando Cirillo

Dr
Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
Naples, Campania, Italy
IF

Ignazio Frangipane

Dr
Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
Naples, Campania, Italy
PC

Paolo Conca

Dr
Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
Naples, Campania, Italy
EC

Ernesto Cimino

Dr
Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
Naples, Campania, Italy

Presenting Author(s)

Antonella Tufano, MD, PhD (she/her/hers)

Professor
Department of Clinical Medicine and Surgery, University of Naples, Federico II
NA, Campania, Italy

Background: Fibrinogen, a 340 kDa glycoprotein, consists of three homologous polypeptide chains (Aɑ, Bß, 𝛾), encoded by FGA, FGB, and FGG genes, respectively, clustered on the long arm of chromosome 4. Congenital fibrinogen disorders are quantitative (afibrinogenemia and hypofibrinogenemia) or qualitative (dysfibrinogenemia or hypo-dysfibrinogenemia). Clinical manifestations include arterial and venous thrombosis, in addition to bleeding. Hypo-dysfibrinogenemia is characterized by low circulating levels of a dysfunctional protein, and shares features of both hypo- and dysfibrinogenemia.

Aims: We report a novel missense mutation in the FGG gene in a family with hypo-dysfibrinogenemia, arterial thromboembolism, and bleeding events.

Methods: Clotting assays, as PT, aPTT, TT, Clauss fibrinogen and immuno-turbidimetric assay for antigenic fibrinogen, were assessed using an ACL TOP 550 spectrophotometric equipment (IL, Bedford, MA, USA). To provide more information on the global coagulation process, we evaluated Rotational Thromboelastometry on whole citrated blood with a computerized ROTEM Delta device (IL, GmbH, Munich, Germany). For genetic analysis, the purified genomic DNA extracted was amplified by PCR and sequencing was performed to find the causative mutation.

Results: We studied a 60-year-old female patient with abnormal bleeding after two caesarean sections with subsequent hysterectomy. The clinical history included arterial hypertension, dyslipidemia, polycythemia, and smoking habit. Laboratory showed a prolonged PT (PT INR:1,25), with normal aPTT. Coagulation factor VII was normal, and fibrinogen was 25 mg/dl, estimated by functional Clauss assay, while antigenic fibrinogen was 156 mg/dl. We identified eight living family members with hypo dysfibrinogenemia through the birth registry office. All had the same missense mutation c.952G>T in exon 8 of gene FGG in heterozygosity. One family member had arterial thrombosis, and, in another member, clinical history was positive for cerebral ischemia. The other members were asymptomatic for thrombosis.

Conclusion(s): We have identified a novel missense mutation in the FGG gene associated with hypo dysfibrinogenemia, thrombosis, and bleeding.