42 research outputs found
Congenital antithrombin deficiency in patients with splanchnic vein thrombosis
Splanchnic vein thromboses (SVT) are a rare condition that can be life-threatening. The most severe thrombophilia associated to SVT is antithrombin (AT) deficiency, usually caused by SERPINC1 mutations. Although transitory AT deficiencies and congenital disorders of the N-glycosylation pathways (CDG) have been recently reported as causes of AT deficiency, the current AT clinical screening still only includes anti-FXa activity. This study aims to 1) improve the detection of antithrombin deficiency in SVT and 2) characterize the features of antithrombin deficiency associated with SVT.The study was performed in 2 cohorts: 1) 89 SVT patients with different underlying etiologies but in whom AT deficiency had been ruled out by classical diagnostic methods; and 2) 271 unrelated patients with confirmed AT deficiency and venous thrombosis. Antithrombin was evaluated by functional (anti-FXa and anti-FIIa) and immunological methods (ELISA, crossed immunoelectrophoresis, western blot), and SERPINC1 sequencing was performed.In 4/89 patients (4.5%) additional alterations in AT were found (two had SERPINC1 mutations, one had a specific variant causing transient AT deficiency and one patient had CDG). In 11 of the 271 patients (4.1%) with AT deficiency and thrombosis, thrombosis was located at the splanchnic venous territory.AT deficiency may be underdiagnosed by current clinical screening techniques. Therefore, a comprehensive AT evaluation should be considered in cases of rethrombosis or doubtful interpretation of anti-FXa activity levels. SVT is a relatively common localization of the thrombotic event in patients with congenital AT deficiency.© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Identificación de nuevos elementos implicados en la regulación de antitrombina= Identification of new elements involved in antithrombin regulation.
Resúmenes de 150 palabras en Inglés
Deficiency of antithrombin caused by mutations affecting the gene encoding this key
anticoagulant (SERPINC1) significantly increases the risk of thrombosis. We aim to
identify new mechanisms involved in antithrombin deficiency. Using molecular,
cellular and biochemical methods, we studied 29 patients with antithrombin deficiency
without SERPINC1 mutation, a family study, three case-control studies including 2,980
patients and 3,996 controls, and two patients with congenital disorder of glycosylation
(CDG). We identified the first mutation affecting the SERPINC1 promoter causing
antithrombin deficiency. We confirmed the low genetic variability of SERPINC1 and its
minor role on the heritability of antithrombin. Genome wide association studies and
silencing experiments identified the first modulating gene of antithrombin, LARGE. We
diagnosed a patient with CDG based on his antithrombin deficiency. Finally, we
described a new disorder with identical biochemical features than CDGs, but only
thrombosis, which is caused by a single mutation in PMM2 and concomitant alcohol
consumption.
Key Words: Antithrombin, Thrombosis, CDG, Mutations, SERPINC1
Resumen de 150 palabras en Castellano.
La deficiencia de antitrombina causada por mutaciones en el gen SERPINC1 incrementa
el riesgo trombótico. Nuestro objetivo fue identificar nuevos mecanismos implicados en
la deficiencia de este anticoagulante. Empleando metodología molecular, celular y
bioquímica estudiamos 29 pacientes con deficiencia de antitrombina sin mutaciones en
SERPINC1, un estudio familiar, tres estudios caso-control (2,980 pacientes/3,996
controles) y dos pacientes con trastornos congénitos de glicosilación (CDG).
Identificamos la primera mutación en el promotor de SERPINC1 que causa deficiencia
de antitrombina. Confirmamos la baja variabilidad genética en SERPINC1 y su escasa
influencia en la heredabilidad de antitrombina. Un GWAS y experimentos de
silenciamiento mostraron que LARGE es el primer gen modulador de antitrombina.
Diagnosticamos un CDG por la deficiencia de antitrombina de un paciente con
trombosis recurrente y descubrimos nuevo desorden con patrón bioquímico similar al
CDG pero solo con trombosis que es causado por una sola mutación en PMM2 y
consumo de alcohol.
Palabras clave: Antitrombina, Trombosis, CDG, Mutaciones, SERPINC
New SERPINC1 gene mutations in patients with antithrombin deficiency : antithrombin Lodz I, II, III, and IV
Identification of a New Mechanism of Antithrombin Deficiency Hardly Detected by Current Methods : duplication of SERPINC1 Exon 6
Functional, biochemical, molecular and clinical characterization of antithrombin c.1157T>C (p.Ile386Thr), a recurrent Polish variant with a founder effect
[Prunus sp.]
原著和名: [記載なし]科名: バラ科 = Rosaceae採集地: 千葉県 千葉市 千葉大学 (下総 千葉大学)採集日: 1982/3/8採集者: 萩庭丈壽整理番号: JH035449国立科学博物館整理番号: TNS-VS-98544