title: A novel fibrinogen B beta chain frameshift mutation causes congenital afibrinogenaemia.
abstract: Congenital afibrinogenaemia is a rare autosomal recessive disorder caused by various mutations within the fibrinogen genes FGA, FGB and FGG. Ins/del mutations in FGB are extremely rare. We report a patient with afibrinogenaemia who suffered from umbilical cord bleeding and repeated bleeding episodes. His plasma fibrinogen levels could not be detected using the Clauss method and immunological methods. Molecular analyses revealed homozygosity in a novel four bases insertion in codon 40 of FGB exon 2 (g. 2833_2834 ins GTTT), which resulted in a truncated 50-residue polypeptide that contained 11 exceptional abnormal residues. In the transient expression experiments, mutant fibrinogen could be detected at higher level than wild-type fibrinogen in COS-7 cell lysates but not in culture media. These results suggest that the homozygous mutation in FGB could be responsible for congenital afibrinogenaemia in this patient. This frameshift mutation could impair fibrinogen assembly and secretion without influencing the protein synthesis.
authors.affiliation: Prof. Zhaoyue Wang, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Zhaoyue
authors.initials: Z
authors.lastname: Wang
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Yu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Bai
authors.forename: Changgeng
authors.initials: C
authors.lastname: Ruan
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000151:congenital* / Q000235:genetics; D000818:Animals; D001777:Blood Coagulation / Q000235:genetics; D019556:COS Cells; D002681:China; D002522:Chlorocebus aethiops; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D016368:Frameshift Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree; D055503:Protein Multimerization / Q000235:genetics; D055815:Young Adult
chemical_list: C115499:BBeta fibrinogen; D005340:Fibrinogen