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Hamostaseologie 1998; 18(03): 107-120
DOI: 10.1055/s-0038-1655341
DOI: 10.1055/s-0038-1655341
Übersichtsarbeiten/Review Articles
Molekulare Grundlagen der Hämophilie A
Further Information
Publication History
Publication Date:
27 June 2018 (online)
Zusammenfassung
Die Hämophilie ist die häufigste genetisch bedingte Form einer schweren Blutungsneigung. Ursächlich für die Erkrankung sind Defekte im Faktor-Vlll-Gen bei den betroffenen Patienten, welche zu einer Verminderung der Faktor-Vlll- Aktivität, mit einer vom Ausmaß der Störung abhängigen Blutungsneigung führen. Nachdem zunächst die Größe des Faktor-Vlll-Gens die Mutationssuche bei den Patienten sehr erschwert hatte, können seit kurzem die für die Erkrankung ursächlichen Gendefekte routinemäßig identifiziert werden. Dies hat zu entscheidenden Verbesserungen in der Diagnostik und dem Verständnis der Pathogenese der Hämophilie-A-Erkrankung geführt. So ist nach Identifizierung des Gendefektes in einer betroffenen Familie für alle Ratsuchenden eine schnelle und sichere Konduktorinnendiagnostik möglich. Die Korrelation des Gendefektes mit dem klinischen Verlauf der Patienten hat gezeigt, daß die Art der Mutation einen wichtigen genetischen Prädispositionsfaktor für die heutzutage schwerste Komplikation der Hämophilie-Behandlung, die Hemmkörperbildung, darstellt. Ein kürzlich entwickeltes molekulares Modell des Faktor-Vlll- Proteins erlaubt die gezielte Untersuchung der Auswirkungen einer Mutation auf das Faktor-VlII-Molekül und hat neue Erkenntnisse über die Wechselwirkungen von Faktor VIII mit anderen Faktoren der Gerinnungskaskade hervorgebracht.
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