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Hamostaseologie 2015; 35(S 01): S22-S26
DOI: 10.1055/s-0037-1619825
Case report
Schattauer GmbH

Novel point mutation in fibrinogen (Innsbruck; BβArg44Gly)

Phenotypic differences compared to another mutation (fibrinogen Nijmegen) at the same positionNeue Punktmutation (Fibrinogen Innsbruck; BβArg44Gly)Phänotypische Abweichung im Vergleich zu einer anderen Mutation (Fibrinogen Nijmegen) an gleicher Position
P. Würtinger
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
,
A. Griesmacher
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
,
V. Ivaskevicius
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
2   Institute of Experimental Haematology and Transfusion Medicine and the Haemophilia Centre, University Clinic Bonn, Germany
,
A. Biswas
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
2   Institute of Experimental Haematology and Transfusion Medicine and the Haemophilia Centre, University Clinic Bonn, Germany
,
S. Zehetbauer
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
3   Division of Child and Adolescent Psychiatry, Medical University of Innsbruck, Austria
,
J. Oldenburg
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
2   Institute of Experimental Haematology and Transfusion Medicine and the Haemophilia Centre, University Clinic Bonn, Germany
,
K. Hohenstein
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
,
G. Weigel
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
1   Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Austria
› Author Affiliations
Further Information

Publication History

received: 03 March 2015

accepted in revised form: 09 July 2015

Publication Date:
28 December 2017 (online)

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Summary

This is a report of a novel fibrinogen point mutation (fibrinogen Innsbruck), a C/G point mutation at position 220 of exon two of the fibrinogen B|-chain leading to B|3Arg44Gly. The heterozygous mutation was found in a 16-year-old adolescent, hospitalized for the management of juvenile depression, who suffered from multiple epistaxis episodes during his stay at the university hospital in Innsbruck, Austria. Fibrinogen (based on the Clauss method) and fibrinogen antigen levels were highly discrepant (86 vs. 223 mg/dl) with thrombin time and reptilase time being in the respective upper reference ranges. Densitometric analysis of electrophoretic band pattern showed a reduction of a-polymers, indicating an impaired fibrin polymerization. This is in agreement with structural analysis, which showed a disturbance of the flexibility and structure of the region surrounding the fibrinoeptide B cleavage site. Fibrinogen Nijmegen, a mutation at the same position, is causative for thrombosis, whereas fibrinogen Innsbruck appears to lead to a bleeding tendency, illustrating that even mutations at the same position can cause contrary symptoms.

Zusammenfassung

Wir berichten von einer neuen Fibrinogen-Punktmutation (Fibrinogen Innsbruck). Es handelt sich um eine C/G-Mutation an Position 220 im Exon zwei der Fibrinogen B|-Kette, die zum Basen-austausch B(3Arg44Gly führt. Die heterozygote Mutation wurde bei einem 16-Jährigen gefunden, der wegen einer juvenilen Depression stationär im Universitätskrankenhaus Innsbruck aufgenommen worden war. Während seines Krankenhausaufenthalts kam es zu mehreren Epistaxis-Episoden. Der Fibrinogenspiegel (Clauss-Methode) war stark diskrepant zur Fi-brinogen-Antigen-Konzentration (86 vs. 223 mg/dl) bei einer Thrombin- and Reptilase-Zeit im jeweils oberen Referenzbereich. Die densito-metrische Analyse des Bandenmusters der Gel-elektrophorese zeigte eine starke Reduktion der a-Polymere, was auf eine gestörte Fibrin-Polymerisation hindeutet. Dieses Resultat wird durch die Strukturanalyse gestützt, welche Struktur- und Flexibilitätsstörungen im Bereich der Spaltstelle von Fibrinogen B zeigt. Fibrinogen Nijmegen, eine Mutation an derselben Position, ist der Auslöser von Thrombosen, wohin-gegen Fibrinogen Innsbruck zu einer erhöhten Blutungsneigung zu führen scheint. Diese Ergebnisse zeigen, dass sogar Mutationen an derselben Stelle zu unterschiedlichen klinischen Symptomen führen können.

Keywords

Fibrinogen - congenital dysfibrinogenemia - fibrinogen mutation

Schlüsselwörter

Fibrinogen - kongenitale Dysfibrinogenämie - Fibrinogen-Mutation
 

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