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A novel variant in Serpina7 gene in a family with thyroxine-binding globulin deficiency

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Abstract

Thyroxine-binding globulin (TBG) carries approximately 75% of serum T4 and T3. This protein is encoded by serpina7 gene, formerly known as TBG gene, localized on X-chromosome (Xq22.2). A deficiency in TBG is suspected when abnormally low serum total T4 and T3 are encountered in clinically euthyroid subjects in the presence of normal serum TSH. This condition has been associated with different serpina7 gene mutations resulting in amino acid substitutions or truncations in the mature protein. Herein, we report a new serpina7 gene variant in three members of the same family. It results in the replacement of the normal asparagine 233 by isoleucine and, subsequently, in disruption of a glycosylation site. Co-segregation of this new variant with undetectable levels of TBG in the hemizygous man studied and failure to recognize the same variant in 100 alleles at random, made us to consider it as the underlying cause of the TBG deficiency.

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Authors and Affiliations

  1. Molecular Pathobiology Research Center, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E, Lisbon, Portugal

    Rita Domingues & Maria João Bugalho

  2. Endocrinology Laboratory, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E, Lisbon, Portugal

    Paula Font

  3. Department of Endocrinology, Portuguese Institute of Oncology of Lisbon Francisco Gentil, E.P.E, Lisbon, Portugal

    Luís Sobrinho & Maria João Bugalho

  4. Faculty of Medical Sciences, New University of Lisbon, Lisbon, Portugal

    Luís Sobrinho & Maria João Bugalho

  5. Centro de Investigação de Patobiologia Molecular (CIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E, R. Professor Lima Basto, 1099-023, Lisbon, Portugal

    Rita Domingues

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  1. Rita Domingues
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  2. Paula Font
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  3. Luís Sobrinho
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  4. Maria João Bugalho
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Correspondence to Rita Domingues.

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Domingues, R., Font, P., Sobrinho, L. et al. A novel variant in Serpina7 gene in a family with thyroxine-binding globulin deficiency. Endocr 36, 83–86 (2009). https://doi.org/10.1007/s12020-009-9202-2

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  • DOI: https://doi.org/10.1007/s12020-009-9202-2

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