Hereditary factor V deficiency from heterozygous mutations with a novel variant p.Pro798Leufs∗13 in the F5 gene

Deng, Yuping; Zhu, Jiajin; Gong, Yingyun; Yi, Xiaoqing; Zhou, Liyan; Xie, Yaosheng; Wang, Mingshan; Wu, Weibing

doi:10.1097/mbc.0000000000001056

Cited by 2 publications

(3 citation statements)

References 16 publications

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“…This may be the reason for the decrease of FV:Ag in p.Asp2222Gly and p.Arg96His heterozygotes. The p.Pro798Leufs Ã 13 was first identified by Deng et al 5 , which suggested that it was a disease-causing mutation and might give rise to damage to the function and structure of the FV protein. According to our protein structure model, the p.Pro798Leufs Ã 13 mutation caused the generation of premature termination of FV protein, subsequently, resulting in the formation of truncated protein.…”

Section: Discussionmentioning

confidence: 99%

“…According to the literature, 5 the calibrated automated thrombin (CAT) generation assay was used to examine thrombin generation. Following the protocol of the Thrombinoscope BV company (Rijswijk, the Netherlands), we measured the lag time, peak height, time to peak (ttPeak), and endogenous thrombin potential (ETP) to evaluate the procoagulant activity of FV on a Fluoroskan Ascent FL reading meter (Thermo Electron and Fisher Scientific Company, Waltham, Massachusetts, United States).…”

Section: Methodsmentioning

confidence: 99%

“…The pathogenicity analyses of p.Pro798Leufs Ã 13 and p.Asp2222Gly were listed in the literature. 5 The protein model analysis of FV by PyMOL software revealed that Ser111 in wild type located in A1 domain formed a hydrogen bond with Tyr66, Gly125, Ser174, and His175, respectively. When Ser111 was mutated to Ile111, the hydrogen bond formed between Ile111 and Gly125 disappeared along with the hydrogen bond between Ile111 and His175.…”

Section: Bioinformatics Analysismentioning

confidence: 99%

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Genetic Analysis of Hereditary Coagulation Factor V Deficiency in Two Chinese Families Caused by Compound Heterozygous Mutations

et al. 2023

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Objective This study aims to provide a preliminary discussion of the molecular basis of FV deficiency caused by compound heterozygous mutations in two Chinese families. Methods Relative coagulation index was measured by the one-stage clotting method and the FV:Ag was measured by ELISA. All exons and flanking regions of the F5 gene were amplified by PCR and directly sequenced. ClustalX-2.1-win was used to analyze the conservation of mutations. The online software was used to predict the pathogenicity of mutations. PyMOL was used to analyze the variation in the spatial structure of the FV protein before and after mutations. Calibrated automated thrombogram was used to analyze the function of the mutant protein. Results Phenotyping suggested that both probands had a simultaneous decrease in FV:C and FV:Ag. Their genetic tests showed that proband A had a missense mutation p.Ser111Ile in exon 3 and a polymorphism p.Arg2222Gly in exon 25. At the same time, the proband B had a missense mutation p.Asp96His in exon 3 and a frame-shift mutation p.Pro798Leufs*13 in exon 13. Meanwhile, the p.Ser111Ile is conserved among homologous species. The bioinformatics and protein model analysis revealed that p.Ser111Ile and p.Pro798Leufs*13 were pathogenic and could affect the structure of the FV protein. The thrombin generation test revealed that the clotting function of proband A and B had been affected. Conclusion These four mutations may be responsible for the reduction of FV levels in two Chinese families. Moreover, the p.Ser111Ile mutation is a novel pathogenic variant that has not been reported.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Bioinformatics Analysismentioning

confidence: 99%

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Genetic Analysis of Hereditary Coagulation Factor V Deficiency in Two Chinese Families Caused by Compound Heterozygous Mutations

et al. 2023

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Genetic analysis of a pedigree with hereditary coagulation factor XII deficiency

Fang,

Chen,

Zou

et al. 2024

Preprint

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Objective: Analyze the clinical phenotype and gene mutations of a family with hereditary FXII deficiency, and preliminarily explore its molecular pathogenic mechanism. Methods: The routine coagulation indicators and related coagulation factors were measured.. Thromboelastography and thrombin generation tests simulated coagulation and anticoagulation states in vitro and in vivo. PCR direct sequencing was utilized to analyze all exons and flanking sequences of the F12 gene in the proband, confirming suspected mutations through reverse sequencing, and identifying corresponding mutation sites in family members. Using ClustalX-2.1-win to analyze the conservation of the variant, and employing online software to predict the pathogenicity of mutations. Results: The proband exhibited significantly prolonged APTT (169.1 seconds) and a pronounced decrease in FXII:C to 1.0%. Thromboelastography testing indicated a diminished function of the endogenous coagulation system, while thrombin generation testing revealed a normal ability for thrombin production in the proband. Gene sequencing revealed that the proband harbored a deletion mutation c.303_304delCA in exon 5 and a substitution mutation c.800+1G>A in intron 8. All three bioinformatics software indicated that the mutations were pathogenic and could lead to the production of a terminator, potentially altering the structure and function of the protein. Conclusion: The deletion mutation c.303_304delCA and substitution mutation c.800+1G>A are associated with a decreased in FXII levels in this family, with the c.800+1G>A mutation being the first reported mutation worldwide.

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Hereditary factor V deficiency from heterozygous mutations with a novel variant p.Pro798Leufs∗13 in the F5 gene

Cited by 2 publications

References 16 publications

Genetic Analysis of Hereditary Coagulation Factor V Deficiency in Two Chinese Families Caused by Compound Heterozygous Mutations

Genetic Analysis of Hereditary Coagulation Factor V Deficiency in Two Chinese Families Caused by Compound Heterozygous Mutations

Genetic analysis of a pedigree with hereditary coagulation factor XII deficiency

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