title: A codon 338 nonsense mutation in the factor IX gene in unrelated hemophilia B patients: factor IX338 New York.
abstract: Hemophilia B is an X-linked recessive bleeding disorder resulting from a deficiency of the coagulation factor IX (FIX) protein activity, a vitamin K-dependent serine protease active in both the intrinsic and extrinsic coagulation systems. DNA analyses of the factor IX gene in two unrelated patients with severe hemophilia B, with a IX coagulant activity less than 1% and undetectable FIX antigen, detected the loss of the second TaqI site in exon h (VIII) in both individuals. Polymerase chain reaction (PCR) amplification of 576 base pairs of exon h (VIII) with cloning and dideoxy sequencing of cloned DNA from one hemophiliac revealed a single C----T transition in codon 338 that changes an arginine residue codon CGA to a nonsense codon TGA. Allele-specific oligonucleotide probe hybridization with a mutant (C----T) and a wild-type allele confirmed the same mutation in amplified genomic DNA of the second hemophilia patient. The C----T transition represents another example of mutation at a CpG dinucleotide. DNA polymorphism analysis of the FIX gene in both individuals revealed each to be on a separate FIX haplotype; therefore, predicting each to be a separate mutation event.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: M C
authors.initials: MC
authors.lastname: Driscoll
authors.forename: E
authors.initials: E
authors.lastname: Bouhassira
authors.forename: L M
authors.initials: LM
authors.lastname: Aledort
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon / Q000235:genetics*; D004252:DNA Mutational Analysis; D005164:Factor IX / Q000235:genetics* / Q000302:isolation & purification; D005784:Gene Amplification; D005796:Genes; D006580:Genetic Carrier Screening; D002836:Hemophilia B / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: D003062:Codon; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D005164:Factor IX