title: Hypofibrinogenemia caused by a nonsense mutation in the fibrinogen Bbeta chain gene.
abstract: Congenital hypofibrinogenemia, fibrinogen Tottori II, caused by a nonsense mutation in the fibrinogen Bbeta chain gene, was found in a 68-year-old Japanese female. The plasma fibrinogen level was 99.2 mg dL(-1) as determined by the thrombin time method. No overt molecular abnormalities were observed in purified patient fibrinogen by SDS-PAGE analysis. After sequencing all exons and exon-intron boundaries of three fibrinogen genes, we found a heterozygous single point mutation of T-->G at position 3356 of the patient fibrinogen Bbeta chain gene. This nucleotide mutation results in a nonsense mutation (TAT sequence for Bbeta 41Tyr to TAG sequence for a translation termination signal). The mutation was confirmed by polymerase chain reaction-restriction fragment length polymorphism analysis, since this nucleotide mutation results in a new NheI recognition sequence at this position. These data indicated that the nonsense mutation of the fibrinogen Bbeta chain gene caused a truncated fibrinogen Bbeta chain, which may not be assembled in the fibrinogen molecule.
authors: Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical School, Tichigi-ken, Japan.
authors: J
authors: J
authors: Mimuro
authors: A
authors: A
authors: Hamano
authors: T
authors: T
authors: Tanaka
authors: K S
authors: KS
authors: Madoiwa
authors: T
authors: T
authors: Sugo
authors: M
authors: M
authors: Matsuda
authors: Y
authors: Y
authors: Sakata
mesh_terms: D000368:Aged; D020147:Coagulation Protein Disorders / Q000151:congenital / Q000235:genetics*; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis / Q000379:methods; D015252:Deoxyribonucleases, Type II Site-Specific; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000235:genetics; D015241:Fibrinogens, Abnormal / Q000235:genetics*; D006801:Humans; D017354:Point Mutation
chemical_list: C115499:BBeta fibrinogen; D018389:Codon, Nonsense; D015241:Fibrinogens, Abnormal; C489711:fibrinogen Tottori II; D005340:Fibrinogen; C067043:endodeoxyribonuclease NheI; D015252:Deoxyribonucleases, Type II Site-Specific