{
    "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.",
    "authors": [
        {
            "affiliation": "State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.",
            "firstname": "Yan",
            "initials": "Y",
            "lastname": "Xia"
        },
        {
            "affiliation": null,
            "firstname": "Qiu-Ya",
            "initials": "QY",
            "lastname": "Lu"
        },
        {
            "affiliation": null,
            "firstname": "Ye-Ling",
            "initials": "YL",
            "lastname": "Lu"
        },
        {
            "affiliation": null,
            "firstname": "Jing",
            "initials": "J",
            "lastname": "Dai"
        },
        {
            "affiliation": null,
            "firstname": "Qiu-Lan",
            "initials": "QL",
            "lastname": "Ding"
        },
        {
            "affiliation": null,
            "firstname": "Xue-Feng",
            "initials": "XF",
            "lastname": "Wang"
        },
        {
            "affiliation": null,
            "firstname": "Xiao-Dong",
            "initials": "XD",
            "lastname": "Xi"
        },
        {
            "affiliation": null,
            "firstname": "Hong-Li",
            "initials": "HL",
            "lastname": "Wang"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00c2\u00a9 2012 Elsevier Inc. All rights reserved.",
    "doi": "10.1016/j.bcmd.2012.02.005",
    "journal": "Blood cells, molecules & diseases",
    "keywords": [],
    "methods": null,
    "publication_date": "2012-03-20",
    "pubmed_id": "22424603",
    "results": null,
    "title": "Molecular basis of type I antithrombin deficiency in two women with recurrent venous thromboembolism in the first trimester of pregnancy.",
    "xml": "<Element 'PubmedArticle' at 0x788502f12f70>"
}