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Thromb Haemost 1990; 63(01): 024-026
DOI: 10.1055/s-0038-1645679
Original Article
Schattauer GmbH Stuttgart

Factor IX Chongqing: a New Mutation in the Calcium-Binding Domain of Factor IX Resulting in Severe Hemophilia B

N S Wang
The Department of Pediatrics, University of Washington and the Puget Sound Blood Center, Seattle, Washington, USA
,
M Zhang
The Department of Pediatrics, University of Washington and the Puget Sound Blood Center, Seattle, Washington, USA
,
A R Thompson
**   The Department Medicine, University of Washington and the Puget Sound Blood Center, Seattle, Washington, USA
,
S-H Chen
The Department of Pediatrics, University of Washington and the Puget Sound Blood Center, Seattle, Washington, USA
› Author Affiliations
Further Information

Publication History

Received 05 June 1989

Accepted after revision 04 October 1989

Publication Date:
02 July 2018 (online)

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Summary

A Chinese patient with sporadic, severe hemophilia B was found to have a low level of total factor IX antigen (3.5 U/dl), but less apparent antigen in an assay using a calcium-dependent antibody fraction (1.1 U/dl). This suggested a defect in the factor IX Gla domain coded mainly by exon 2 of the factor IX gene. Exon 2 was therefore amplified and sequenced. An A to T substitution was found at nucleotide 6455 of the patient’s factor IX gene. This transversion changes the codon for Glu 27 in normal factor IX to a codon for Val. Since Glu 27 becomes an essential Gla residue, the defect should result in altered calcium-binding or calcium-dependent conformation of the patient’s factor IX. The introduction of a hydrophobic side chain also appears to affect the hemophilic protein’s stability.

In leukocyte DNA from the patient’s mother, the nucleotide sequence of exon 2 was entirely normal. Thus, barring somatic mosaicism within her germ cells, the new mutation occurred in oogenesis of her ovary.

Keywords

Hemophilia B - Factor IX - Calcium-binding - Polymerase chain reaction
 

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