The CDC Hemophilia B mutation project mutation list: a new online resource

Tengguo Li,Connie H Miller,Amanda B Payne,W Craig Hooper

doi:10.1002/mgg3.30

Abstract

Hemophilia B (HB) is caused by mutations in the human gene F9. The mutation type plays a pivotal role in genetic counseling and prediction of inhibitor development. To help the HB community understand the molecular etiology of HB, we have developed a listing of all F9 mutations that are reported to cause HB based on the literature and existing databases. The Centers for Disease Control and Prevention (CDC) Hemophilia B Mutation Project (CHBMP) mutation list is compiled in an easily accessible format of Microsoft Excel and contains 1083 unique mutations that are reported to cause HB. Each mutation is identified using Human Genome Variation Society (HGVS) nomenclature standards. The mutation types and the predicted changes in amino acids, if applicable, are also provided. Related information including the location of mutation, severity of HB, the presence of inhibitor, and original publication reference are listed as well. Therefore, our mutation list provides an easily accessible resource for genetic counselors and HB researchers to predict inhibitors. The CHBMP mutation list is freely accessible at http://www.cdc.gov/hemophiliamutations.

Highlights

Hemophilia is a disorder characterized by defective blood clotting, which is classified as Hemophilia A or B and is X-linked recessive, affecting primarily males (Bowen 2002)
Hemophilia B (HB), known as Christmas disease, is caused by mutations in the gene F9, which is located at the distal end of the long arm of the X chromosome (Yoshitake et al 1985)
We describe the Centers for Disease Control and Prevention (CDC) Hemophilia B Mutation Project (CHBMP) mutation list containing more than 1000 unique mutations

Summary

Introduction

Hemophilia is a disorder characterized by defective blood clotting, which is classified as Hemophilia A or B and is X-linked recessive, affecting primarily males (Bowen 2002). F9 encodes coagulation factor IX (FIX), a serine protease functioning as a blood clotting factor, which is mainly expressed in liver cells (Anson et al 1984). Upon the activation by factor XIa of the intrinsic coagulation pathway or by the tissue factor/FVIIa complex of the extrinsic pathway, the activation peptide in the middle of the protein (residues 146– 180) is cleaved out to give rise to a mature protein, an active serine protease (FIXa) composed of a light chain and a heavy chain linked by a single disulfide bond (Kurachi and Davie 1982; Taran 1997). FIXa participates in the blood clotting process through cleavage of an arginine–isoleucine bond of factor X to form activated factor X (FXa) in the coagulation cascades (Zhong et al 2002).

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