Factor IX Chongqing: a new mutation in the calcium-binding domain of factor IX resulting in severe hemophilia B.
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.
Wang
N S
NS
Department of Pediatrics, University of Washington, Seattle.
Zhang
M
M
Thompson
A R
AR
Chen
S H
SH
D000595:Amino Acid Sequence; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002648:Child; D005091:Exons; D005164:Factor IX / Q000235:genetics*; D002836:Hemophilia B / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation
D002135:Calcium-Binding Proteins; C063858:factor IX Chongqing; D005164:Factor IX