Fibrinogen Seoul (FGG Ala341Asp): a novel mutation associated with hypodysfibrinogenemia.
Dysfibrinogenemia is a coagulation disorder caused by a variety of structural abnormalities in the fibrinogen molecule that result in fibrinogen function. The molecular basis of hypodysfibrinogenemia was investigated in a 66-year-old woman with peripheral artery obstructive disease and in her family members. Plasma level of functional fibrinogen determined using the Clauss method was lower (75 mg/dL; normal, 140-460 mg/dL) than that measured with immunologic nephelometric assay (137 mg/dL; normal, 180-400 mg/dL). Similar results were also observed in two family members through two generations. DNA was extracted from whole blood, and the coding regions and intron/exon boundaries of gamma chain gene (FGG) were amplified. A novel (Fibrinogen Seoul) heterozygous FGG mutation (GCT->GAT, Ala341Asp) was identified in all three affected family members. Thrombin-catalyzed polymerization was found to be defective on the analysis of purified fibinogen from the propositus. Molecular modeling also showed a conformational change of fibrinogen structure.
Song
Kyung Soon
KS
Department of Laboratory Medicine Seoul, Korea. kssong@yumc.yonsei.ac.kr
Park
Noh Jin
NJ
Choi
Jong Rak
JR
Doh
Hyun Joo
HJ
Chung
Kwang Hoe
KH
D000368:Aged; D001157:Arterial Occlusive Diseases; D001778:Blood Coagulation Disorders / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D015241:Fibrinogens, Abnormal / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D016491:Peripheral Vascular Diseases; D011487:Protein Conformation
D015241:Fibrinogens, Abnormal