A new mutation in the HNF4 binding region of the factor VII promoter in a patient with severe factor VII deficiency.
Investigation of the molecular basis of a severe factor VII (fVII) deficiency revealed compound heterozygosity in the fVII gene. On the paternal allele the patient had 3 structural gene abnormalities frequently associated with fVII deficiency. A new mutation, a C to T transition at position -55 relative to the translational start site, was found on the maternal allele. The study demonstrates that this mutation partially impeded binding of the transcriptional activator, hepatic nuclear factor 4, to the fVII promoter while greatly reducing reporter gene expression in hepatic cells. (Blood. 2000;96:4370-4372)
Carew
J A
JA
Hematology-Oncology Section, Boston VA Healthcare System, Boston, MA, USA.
Pollak
E S
ES
Lopaciuk
S
S
Bauer
K A
KA
D000328:Adult; D019943:Amino Acid Substitution; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites; D001667:Binding, Competitive; D002478:Cells, Cultured; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000235:genetics*; D016368:Frameshift Mutation; D005838:Genotype; D051557:Hepatocyte Nuclear Factor 4; D006579:Heterozygote; D006801:Humans; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D017354:Point Mutation; D011044:Poland; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D003062:Codon; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D005167:Factor VII