[Pathogenesis study of inherited dysfibrinogenemia].
OBJECTIVE
To explore the pathogenesis of a family with inherited dysfibrinogenemia.


METHODS
Coagulation parameters of peripheral venous blood of a family with inherited dysfibrinogenemia from November 2012 were measured. And platelet and fibrinogen functions were examined by thromboelastogram. The antigen concentration of fibrinogen was detected by immune nephelometry. All exons and exon-intron boundaries of FGA, FGB and FGG were amplified and subjected to mutation screening by direct/reverse sequencing. And the influences of mutant fibrinogen structure and function were analyzed and predicated by a molecular structure model.


RESULTS
The values of activated partial thromboplastin time (APTT), D-dimer and fibrinogen antigen of the propositus and his mother (I-2), younger brother (II-3), younger sister (II-2) and daughter (III-1) were all in normal reference value ranges.However thrombin time (TT) was significantly prolonged and the activity of fibrinogen was much lower compared to its antigenicity. Thromboelastogram indicated normal function of platelet and impaired function of fibrinogen of I-2, II-2 and III-1.However the fibrinogen functions of proband and II-3 became much more impaired. Mutation screening demonstrated the homozygous mutation of proband and II-3 while I-2, II-2 and III-1 showed heterozygous mutation of FGG c.1001 A>C (p. Asn308Thr). No mutation was detected among other family members and reducing SDS-PAGE immunoblot showed no variants. Asn308, located at the interface of fibrinogen dimmer, participated in the fibrous structure assembling from the structure model. And mutation at this position will affect the stability of fiber structure.


CONCLUSIONS
FGG c.1001 A>C mutation may account for dominant genetic dysfibrinogenemia in these family members.
Department of Laboratory Medicine, Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310009, China.
Zhaoping
Z
Liao
Siqi
S
Xu
Huqiang
H
Tang
Yiyi
Y
Xie
Xiuzhi
X
Duan
Chunhua
C
Liu
Yue
Y
Cheng
Yuhua
Y
Chen
Deqiang
D
Wang
Miao
M
Luo
Email: zrtzh@zju.edu.cn.
Zhihua
Z
Tao
D000347:Afibrinogenemia / Q000209:etiology* / Q000235:genetics*; D005260:Female; D015241:Fibrinogens, Abnormal; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
D015241:Fibrinogens, Abnormal