Novel mutation in coagulation factor VII (Carmel mutation): Identification and characterization

Cassel, Aliza; Rosenberg, Nurit; Muhammad, Emad; Livnat, Tami; Dardik, Rima; Berl, Miriam; Preis, Meir

doi:10.1002/rth2.12407

Cited by 4 publications

(3 citation statements)

References 31 publications

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“…Previously published articles revealed that the hemorrhagic diathesis in severely affected compound heterozygotes was variable and did not always correlate with the low FVII activity documented [16]. This was also the case in our patients, presenting as asymptomatic during the perioperative period despite an exclusively dysfunctional FVII in their plasma, suggesting a less link between FVII activities and bleeding tendency (see Table 1).…”

Section: Discussionsupporting

confidence: 66%

Phenotypic and genotypic characterization of two factor VII deficiency patients from southeastern China

Wang¹,

Su²,

Chen³

et al. 2022

Blood Coagulation &Amp; Fibrinolysis

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The congenital factor VII deficiency (FVIID) is a rare autosomal recessive haemorrhagic disease caused by mutations in the F7 gene. The aim of this study was to identify the mutations causing FVII deficiency and explain the genotype-phenotype association in two unrelated Chinese patients. Mutation detection was conducted by sequencing the whole F7 gene coding exons, exon-intron boundaries and the untranslated regions of 3 0 and 5 0 . Then, the genetic information was analyzed to predict the structures of the mutated proteins. A total of four different mutations were detected, including three missense mutations (c.64G>A, c.286A>G, and c.722C>A, predicting p. Gly22Ser, p.Arg96Gly, p.Thr241Asn, respectively) and one insertion mutation (c.204_205insCGGC, predicting p. Leu68Argfs M 37), among which two were reported for the first time (p.Arg96Gly, p.Leu68Argfs M 37). Multiple sequence alignments of FVII protein revealed that the residues p. Arg96 and p.Thr241 were highly conserved. The novel missense mutation p.Arg96Gly was determined as damaging with online software Polyphen-2 and SIFT. We investigated two asymptomatic patients diagnosed with severe FVII deficiency and identified two novel mutations (the mutation p.Arg96Gly and p.Leu68Argfs M 37). Identification of the F7 mutations was important for genetic counseling and accurate prediction of the inheritance pattern.

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Section: Discussionsupporting

confidence: 66%

Phenotypic and genotypic characterization of two factor VII deficiency patients from southeastern China

Wang¹,

Su²,

Chen³

et al. 2022

Blood Coagulation &Amp; Fibrinolysis

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“…Полиморфизм гена FVII заключается в замене G на А в позиции 10976, что приводит к изменению биохимических свойств F7, в котором происходит замена аминокислоты Arg на Gln в позиции 353. Полиморфизм 10976 G/A FVII приводит к снижению активности и секреции FVII в кровь [25].…”

Section: генunclassified

Molecular and Genetic Risk Factors for Forming Central Nervous System Damage during Perinatal Period in Preterm Infants. A Review

Лямцева¹,

Костюк²,

Жевнеронок³

et al. 2023

Педиатрия. Восточная Европа

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Недоношенные дети имеют высокий риск повреждения головного мозга в перинатальном периоде, в том числе с формированием структурных и микроструктурных изменений, приводящих в последующем к долгосрочным неблагоприятным неврологическим нарушениям. Доминирующими поражениями центральной нервной системы в перинатальном периоде у недоношенных детей, выступающими в качестве предикторов неврологических и психоречевых нарушений, являются внутрижелудочковые кровоизлияния и повреждение белого вещества головного мозга, включая его наиболее частую форму – перивентрикулярную лейкомаляцию. Недоношенные дети с одинаковыми сроками гестации и длительностью нахождения на ИВЛ имеют значительную вариабельность по развитию внутричерепных кровоизлияний и лейкомаляции. В ряде случаев указанная патология, выявленная сразу после рождения, не всегда объясняется внутриутробной инфекцией или воздействием экзогенных перинатальных факторов. В настоящее время широко обсуждается необходимость выявления генетических факторов предрасположенности к перинатальному повреждению головного мозга и перивентрикулярной лейкомаляции, исследуется роль генетической изменчивости медиаторов воспаления и белков свертывания крови в их патогенезе. В статье представляются и анализируются международные обзорные данные о полиморфизме генов факторов свертывания крови FII (20210 G/A), FV (1691 G/A), FVII (10976 G/A), FXIII (13 G/T) и воспалительных цитокинах TNF-α (1031 T/C), IL-1β (511 C/T), IL-10 (1082 G/A), которые могут модифицировать предрасположенность к воспалению, способствовать развитию внутрижелудочковых кровоизлияний, перивентрикулярной лейкомаляции и нарушению развития нервной системы. Перинатальное воздействие инфекции на центральную нервную систему может приводить к ее серьезным структурным повреждениям, в том числе к ВЖК и лейкомаляции. Однако результаты опубликованных работ показывают и роль генетической изменчивости медиаторов воспаления и белков свертывания крови в их патогенезе. Противоречивые результаты исследований больше свидетельствуют об их вторичной роли, возможно, отягощающей степень, выраженность церебрального повреждения и реакцию глиальных элементов на воспаление. Изучение генетических полиморфизмов как факторов риска в развитии перинатального повреждения головного мозга пока не дает сделать вывод об их влиянии на исходы неврологического развития недоношенных детей, однако, по нашему мнению, перинатальное повреждение головного мозга и ПВЛ у недоношенных детей может быть результатом взаимодействия полиморфных генов, связанных с воспалительной реакцией и генетически-средовыми факторами. Дальнейший поиск и выявление наиболее значимых взаимодействий может открыть новые перспективы для разработки новых стратегий в лечении и абилитации недоношенных новорожденных. Premature babies have a high risk of brain damage in the perinatal period, including those forming structural and microstructural changes, leading subsequently to long-term adverse neurological disorders. Predominant lesions of the central nervous system in the perinatal period in premature infants appearing as predictors of neurological and psychoverbal disorders are intraventricular hemorrhages and damage to the white matter of the brain, including its most frequent form, periventricular leukomalacia. Premature babies with the same gestational age and duration of stay on ALV have significant variability in developing intracranial hemorrhages and leukomalacia. In some cases, the above pathology, detected immediately after birth, is not always explained by intrauterine infection or exposure to exogenous perinatal factors. Currently, the need to identify genetic predisposition factors for perinatal brain injury and periventricular leukomalacia is widely discussed, and the role of genetic variability of inflammatory mediators and blood clotting proteins in their pathogenesis is under study. The article presents and analyzes international review data on the polymorphism of genes of blood clotting factors FII (20210 G/A), FV (1691 G/A), FVII (10976 G/A), FXIII (13 G/T) and inflammatory cytokines TNF-α (1031 T/C), IL-1β (511 C/T), IL-10 (1082 G/A), which can modify the susceptibility to inflammation and contribute to intraventricular hemorrhages, periventricular leukomalacia, and neurodevelopmental disorders. Perinatal exposure to the infection in the central nervous system can lead to serious structural damage, including intraventricular hemorrhage and leukomalacia. However, the results of published works also show the role of genetic variability of inflammatory mediators and blood clotting proteins in their pathogenesis. Contradictory research findings are more indicative of their secondary role, possibly aggravating both the degree and severity of cerebral damage and the response of glial elements to inflammation. Studying genetic polymorphisms as risk factors for perinatal brain damage does not yet allow making a conclusion about their influence on outcomes of neurological development in premature infants; however, in our opinion, perinatal brain damage and periventricular leukomalacia in premature infants may be a result of polymorphic genes interaction associated with inflammatory response and with genetic and environmental factors. Further investigation and identification of the most significant interactions may offer new perspectives for elaborating new strategies in the treatment and habilitation of preterm infants.

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“…ELISA technique using monoclonal FVII-specific antibodies can also be used to measure the plasma level of the FVII antigen (68). In patients with severe, mild/moderate, and asymptomatic congenital FVII deficiency, the levels of FVII:Ag and FVII:C are widely overlapping and cannot be used to predict the clinical severity of the disease; thus, collecting a detailed family history is essential (51). However, the FVII:Ag and FVII:C assays allow one to distinguish between CRM -(FVII:Ag and FVII:C reduced with the same ratio), CRM + (a decreased FVII:C with normal FVII:Ag), and CRMred (FVII:Ag reduction but not as much as FVII:C) (5,6,69).…”

Section: Diagnosismentioning

confidence: 99%

Coagulation Factor VII: Genetic, Molecular, and Clinical Characteristics

Mashayekhi

Ghasemi

2022

Trends in Med Sci

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: Coagulation factor VII (FVII) is a vitamin K-dependent serine protease that plays a pivotal role in normal hemostasis. Mature FVII is a glycoprotein comprised γ-carboxyglutamic acid-rich (Gla) domain, two epidermal growth factor (EGF)-like domains, an activation domain, and a serine protease domain. FVII requires proteolytic activation followed by tissue factor (TF) binding for maximal activity. The F7 gene (14.8 kb) is located on 13q34, composed of nine exons and eight introns. The congenital FVII deficiency is a rare coagulopathy with an autosomal recessive pattern of inheritance that occurs due to mutation in the F7 gene. A considerable number of mutations of different types have been identified throughout this gene affecting the expression, structure, and post-translational alterations of the protein. FVII deficiency is the most frequently recessively inherited bleeding disorder. Subjects with FVII deficiency show a wide range of symptoms, including cutaneous hemorrhage, mucosal hemorrhage, gastrointestinal bleeding, joint bleeding, and central nervous system (CNS) hemorrhage. Unlike other coagulation factor deficiencies, serum levels of FVII do not demonstrate the severity of the disease, and there is no direct correlation between serum levels and clinical complications. Replacement therapy is the treatment of choice for FVII deficiency. Various therapeutic products such as prothrombin complex concentrate, plasma-derived FVII concentrate, fresh frozen plasma, and activated recombinant FVII are available to treat FVII deficient individuals. This review aims to provide information on molecular, biochemical, and clinical aspects of coagulation FVII, its role in hemostasis, and the consequences of its deficiency.

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Novel mutation in coagulation factor VII (Carmel mutation): Identification and characterization

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 4 publications

References 31 publications

Phenotypic and genotypic characterization of two factor VII deficiency patients from southeastern China

Phenotypic and genotypic characterization of two factor VII deficiency patients from southeastern China

Molecular and Genetic Risk Factors for Forming Central Nervous System Damage during Perinatal Period in Preterm Infants. A Review

Coagulation Factor VII: Genetic, Molecular, and Clinical Characteristics

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