Thromb Haemost 1991; 66(04): 459-463
DOI: 10.1055/s-0038-1646438
Review Article
Schattauer GmbH Stuttgart

Characterization of Genetic Defects of Hemophilia B of Chinese Origin

Shu-Wha Lin
The Hematology Center and Graduate Institute of Medical Technology, School of Medicine, National Taiwan University, Taipei, Taiwan, ROC
,
Ming-Ching Shen
The Hematology Center and Graduate Institute of Medical Technology, School of Medicine, National Taiwan University, Taipei, Taiwan, ROC
› Author Affiliations
Further Information

Publication History

Received 12 February 1991

Accepted 19 April 1991

Publication Date:
25 July 2018 (online)

Summary

To define the precise genetic defects of hemophilia B of Chinese origin, we have used the polymerase chain reaction (PCR) combined with direct sequencing to analyze the amplified DNA fragments containing the entire coding regions and their flanking introns of the factor IX gene from 6 affected individuals. Among these patients, two are siblings with normal factor IX antigen level (CRM+) yet reduced factor IX clotting activity (28%). Analysis of their factor IX genes revealed a G to A transition at nucleotide residue 10394, which causes substitution of an arginine for a glycine at amino acid residue 48. This is a novel mutation which resides in the first EGF-like domain of factor IX. Studies of two other hemophilia B patients with CRMr phenotypes (factor IX antigen level <35%, and clotting activity <1%), demonstrated a distinct mutation in each individual's factor IX gene. In one case, a guanine to adenine (residue 6365) transition results in replacement of arginine by glutamine at the –4 codon of the propeptide of factor IX. In the other, thymine at 6442 was mutated to cytosine which causes an arginine for cysteine substitution at residue 23. We have also characterized 2 discrete CRM- patients. Both exhibited an identical mutation at nucleotide residue 6460 which generates a translation termination codon (CGA to TGA) at the 29th amino acid. The mutation created a new NlaIII restriction enzyme site which could be used to identify this variant.