[Inherited afibrinogenemia caused by compound heterozygous mutations in the beta beta-chain of fibrinogen].
Congenital afibrinogenemia is a rare autosomal recessive disorder, characterized by the complete absence or extremely reduced level of fibrinogen. To analyze the phenotype and genotype of a family with inherited afibrinogenemia, laboratory studies including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) were tested in the proband and 9 family members. Fibrinogen (Fg) in plasma were measured by both functional and immunoturbidimetry assay. All the exons, exon-intron boundaries and promoter regions of three Fg genes were analyzed by direct sequencing. 102 healthy blood donors were used as normal control. The results showed that phenotype of the proband was diagnosed as afibrinogenemia. Compound heterozygous mutations in Fg FGB gene were detected in the proband. One was a nonsense mutation (Arg17stop) in exon 2, traced back to the proband's mother. The other was a missense mutation (Gly347Arg) in exon 7, which was from the proband' s father. It is concluded that afibrinogenemia is caused by the compound heterozygous mutations Arg17stop and Gly347Arg in the Beta beta-chain of fibrinogen.
Fang
Yi
Y
Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Second Medical University, Shanghai 200025, China.
Wang
Hong-Li
HL
Wang
Xue-Feng
XF
Fu
Qi-Hua
QH
Wang
Wen-Bin
WB
Xie
Shuang
S
Zhou
Rong-Fu
RF
Dai
Jing
J
Wang
Zhen-Yi
ZY
D000328:Adult; D000347:Afibrinogenemia / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D005340:Fibrinogen / Q000737:chemistry / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
C115499:BBeta fibrinogen; D018389:Codon, Nonsense; D005340:Fibrinogen