Molecular basis of type I antithrombin deficiency in two women with recurrent venous thromboembolism in the first trimester of pregnancy.
Blood Cells Mol Dis
; 48(4): 254-9, 2012 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-22424603
ABSTRACT
Inherited antithrombin (AT) deficiency carries a 50% risk of venous thromboembolism (VTE) during pregnancy. Here, we investigated the molecular basis of type I AT deficiency in two women with recurrent VTE in the first trimester of pregnancy. Phenotype analysis showed both probands had almost 50% of normal AT levels. Two novel heterozygous AT mutations were identified g.7920C>T resulting in a Trp225Cys mutation in case 1 and g.13863C>A causing an Ala404Asp mutation in case 2. Transient expression of either wild-type (WT) or mutant AT expression vectors in HEK293T and CHO cells showed impaired secretion of both AT mutant proteins. Immunofluorescence analysis revealed that the staining of AT-Trp225Cys in both endoplasmic reticulum (ER) and Golgi apparatus was similar to that of AT-WT, and the staining of AT-Ala404Asp was mainly present in ER but was weaker than that of AT-WT. These results revealed that the type I AT deficiency in two patients was caused by impaired secretion of the AT-Trp225Cys and AT-Ala404Asp mutant proteins, respectively. The two mutations are associated with a high risk of thrombotic onset and women with these AT mutations are prone to VTE in early pregnancy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Complicaciones Hematológicas del Embarazo
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Antitrombina III
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Deficiencia de Antitrombina III
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Tromboembolia Venosa
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Blood Cells Mol Dis
Asunto de la revista:
HEMATOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
China