Insight into molecular changes of the FIX protein in a series of Italian patients with haemophilia B

Haemophilia : the Official Journal of the World Federation of Hemophilia
M P BicocchiM Acquila

Abstract

Deficiency or dysfunction of factor IX FIX leads to haemophilia B (HB), an X-linked, recessive, bleeding disorder. On a molecular basis, HB is due to a heterogeneous spectrum of mutations spread throughout the F9 gene. In several instances, a cause-effect relation has been elucidated, in others predicted possibilities have been offered by crystallography inspection and by software-constructed models of the protein. The aim of this study was to contribute to the understanding of HB molecular pathology. The F9 missense mutations we identified in 21 unrelated Italian HB patients by direct sequencing of the whole F9 coding regions were inspected for the causative effect they provoked on the ensuing transcript, and on the protein structure. Each alteration was studied in order to: (i) characterize the defect on the basis of the nature of the mutation; (ii) identify the predicted defect that is induced in the gene and (iii) speculate about the potential, detrimental effects which upset the protein functionality through an idealized FIX model. The resulting data may further contribute to the comprehension of the mechanisms underlying the disease.

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Citations

Sep 26, 2013·International Journal of Hematology·Barbara DietrichEva-Maria Muchitsch
May 22, 2013·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Xabier Arias-MorenoJose F Lucía
Nov 28, 2015·Haemophilia : the Official Journal of the World Federation of Hemophilia·A MårtenssonR Ljung
Nov 17, 2007·Haemophilia : the Official Journal of the World Federation of Hemophilia·N A GoldenbergM J Manco-Johnson
Jan 1, 2014·American Journal of Hematology·Tengguo LiW Craig Hooper
Apr 9, 2015·Journal of Thrombosis and Haemostasis : JTH·A C Goodeve
Feb 11, 2015·Expert Review of Clinical Pharmacology·Peter L TurecekFriedrich Scheiflinger

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