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| Analysis of phenotype and genotype in two Chinese pedigrees with inherited hypofibrinogenemia caused by γTrp208Leu |
| 1.Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015; 2.Department of Clinical Laboratory, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027 |
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| Cite this article: |
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YANG Lihong1,HAO Xiuping1,DING Hongxiang2, et al. Analysis of phenotype and genotype in two Chinese pedigrees with inherited hypofibrinogenemia caused by γTrp208Leu[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2015, 45(7): 525-.
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Abstract Objective: To analyze the phenotype and genotype of two Chinese pedigrees with inherited hypofibrinogenemiaidentify by the same mutation. Methods: Laboratory tests, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), plasminogen activity (PLG:C), and fibrinogen degradation products (FDPs) were detected in two pedigrees. The activity and antigen plasma fibrinogen (Fg:C, Fg:Ag) were analyzed by Clauss and immunoturbidimetry methods respectively. All the exons and exon-intron boundaries of the three Fg genes FGA, FGB and FGC were amplified by PCR and followed by direct sequencing. The mutation was analyzed by the Swiss-Model and PIC. Results: Two probands had normal PT, APTT, PLG:A and FDPs, but slightly prolonged TT. The Fg:C of the two probands were significantly reduced, 0.49 g/L and 0.63 g/L respectively. Their Fg:Ag were both significantly reduced, 0.63 g/L and 0.77 g/L respectively. These abnormalities were also found in his grandma and father of proband A, mother, aunt and cousin of proband B. Genetic analysis revealed a heterozygous G>T change at nucleotide 5792 in exon 7 of FGG gene in the two probands, predicting a heterozygous Trp208Leu mutation. Model analysis showed that the Trp208Leu mutation is disrupted the native hydrogen bonding network of Thr314, and changed the molecular geometries, increasing instability of the protein. Conclusion: Inherited hypofibrinogenemia in those two pedigrees were caused by heterozygous Trp208Leu mutation in the γ chain of Fg.
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Received: 10 December 2014
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