Antithrombin deficiency in three Japanese families: One novel and two reported point mutations in the antithrombin gene

Maruyama, Keiko; Morishita, Eriko; Karato, Megumi; Kadono, Tadaaki; Sekiya, Akiko; Goto, Yoshihisa; Satō, Tomomi; Nomoto, Haruka; Omi, Wataru; Tsuzura, Sachie; Imai, Hidenori; Asakura, Hitoshi; Ohtake, Shigeki; Nakao, Shinji

doi:10.1016/j.thromres.2013.06.001

Cited by 11 publications

(4 citation statements)

References 31 publications

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“…SERPINA5 mutations have been linked with increased papillary thyroid cancer risk [76], and mutations in SERPINA10 have been linked to pregnancy complications [77]. Predisposition to familial venous thromboembolic disease has been linked to mutations in SERPINC1 [78,79]. Finally, SNP variants for the SERPING1 gene have been shown to be associated with hereditary angioedema [80].…”

Section: Methodsmentioning

confidence: 99%

Update of the human and mouse SERPINgene superfamily

et al. 2013

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The serpin family comprises a structurally similar, yet functionally diverse, set of proteins. Named originally for their function as serine proteinase inhibitors, many of its members are not inhibitors but rather chaperones, involved in storage, transport, and other roles. Serpins are found in genomes of all kingdoms, with 36 human protein-coding genes and five pseudogenes. The mouse has 60 Serpin functional genes, many of which are orthologous to human SERPIN genes and some of which have expanded into multiple paralogous genes. Serpins are found in tissues throughout the body; whereas most are extracellular, there is a class of intracellular serpins. Serpins appear to have roles in inflammation, immune function, tumorigenesis, blood clotting, dementia, and cancer metastasis. Further characterization of these proteins will likely reveal potential biomarkers and therapeutic targets for disease.

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Section: Methodsmentioning

confidence: 99%

Update of the human and mouse SERPINgene superfamily

et al. 2013

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“…Individuals with this type of antithrombin deficiency typically have normal levels of antithrombin in the plasma, but it does not function properly. Maruyama et al [25] conclude that the Arg 56 Cys mutant is responsible for type II heparin-binding site deficiency. They also hold a view that the Ala 459 Asp and Pro 112 Arg mutants are associated with type I antithrombin deficiency.…”

Section: Serpinc1 and Diseasesmentioning

confidence: 99%

SerpinC1/Antithrombin III in kidney-related diseases

Wang

Liang

2017

Clinical Science

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The gene SerpinC1 encodes a serine protease inhibitor named antithrombin III (ATIII). This protease demonstrates both anticoagulant and anti-inflammatory action. ATIII is the most important coagulation factor inhibitor, and even minor changes in ATIII can significantly alter the risk of thromboembolism. ATIII can also suppress inflammation via a coagulation-dependent or -independent effect. Moreover, apart from ATIII deficiency, ATIII and its gene SerpinC1 may also be related to many diseases (e.g. hypertension, kidney diseases). The present review summarizes how ATIII affects the progress of kidney disease and its mechanism. Further studies are required to investigate how ATIII affects renal function and the treatment.

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“…Detection of this polymorphism was executed by PCR, followed by agarose electrophoresis [26]. Two silent SNPs, rs5877 (c.981A>G, p.Val327=, minor allele frequency [MAF] 0.326) and rs5878 (c.1011A>G, p.Gln337=, MAF 0.332), within exon 5 were determined by direct fluorescent sequencing on an ABI3130 Genetic Analyzer (protocol is available on request) and analyzed by using Sequencing Analysis 5.1.1 software (Life Technologies, Carlsbad, CA, USA) [27].…”

Section: Genetic Studiesmentioning

confidence: 99%

Founder effect is responsible for the p.Leu131Phe heparin‐binding‐site antithrombin mutation common in Hungary: phenotype analysis in a large cohort

Gindele

Oláh

Ilonczai

et al. 2016

Journal of Thrombosis and Haemostasis

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EssentialsAntithrombin Budapest3 (ATBp3; p.Leu131Phe) causing heparin-binding-site defect is common. We studied the clinical and laboratory phenotype of a large Hungarian ATBp3 cohort (n = 102). Founder effect of ATBp3 was confirmed by 12 genetic markers; anti-FXa AT assay was 100% sensitive. The spectrum of thrombotic symptoms was wide in ATBp3 patients including arterial thrombosis.Summary. Background: Antithrombin (AT) is a key regulator of the coagulation. In type II deficiency, the heparinbinding-site defect (type II HBS) is considered to be relatively low thrombosis risk. Objectives: Our aims were to search for SERPINC1 mutation(s) and to describe the clinical and laboratory phenotype of a large number of AT Budapest3 (ATBp3, p.Leu131Phe) carriers and confirm the presence of a founder effect. Patients/Methods: AT-deficient patients were recruited and carriers of ATBp3, n = 102 (63 families) were selected. To investigate the founder effect, eight intragenic single nucleotide polymorphisms, a 5 0 -length dimorphism, and five microsatellite markers were detected. Clinical and laboratory data of the patients were collected and analyzed. Results: In AT deficiency, 16 different causative mutations were found, and the great majority of patients were of type II HBS subtype. Most of them (n = 102/118, 86.5%) carried the ATBp3 mutation. The ATBp3 mutant allele was associated with one single haplotype, while different haplotypes were detected in the case of normal allele. The anti-factor Xabased AT activity assay that we used could detect all ATBp3 patients with high sensitivity in our cohort. ATBp3 homozygosity (n = 26) was associated with thrombosis at a young age and conferred a high thrombotic risk. Half of the heterozygotes (n = 41/76, 53.9%) also had venous and/ or arterial thrombosis, and pregnancy complications were also recorded. Conclusion: In Hungary, the founder mutation, ATBp3, is the most common AT deficiency. Our study is the first in which the clinical characterization of ATBp3 mutation was executed in a large population.

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Antithrombin deficiency in three Japanese families: One novel and two reported point mutations in the antithrombin gene

Cited by 11 publications

References 31 publications

Update of the human and mouse SERPINgene superfamily

Update of the human and mouse SERPINgene superfamily

SerpinC1/Antithrombin III in kidney-related diseases

Founder effect is responsible for the p.Leu131Phe heparin‐binding‐site antithrombin mutation common in Hungary: phenotype analysis in a large cohort

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