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High copper levels and increased elastolysis in a patient with cutis marmorata teleangiectasia congenita

Authors

  • Aleksander Hinek,

    1. Division of Cardiovascular Research, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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  • Shailly Jain,

    1. Divisions of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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  • Glenn Taylor,

    1. Department of Laboratory Medicine and Pathobiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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  • David Nykanen,

    1. Division of Cardiology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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  • David Chitayat

    Corresponding author
    1. Divisions of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
    2. The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
    • Department of Obstetrics and Genecology, The Prenatal Diagnosis and Medical Genetics Program, The Ontario Power Generation Building, 700 University Avenue, Room 3292, Toronto, Ontario, Canada M5G 1Z5.
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  • How to cite this article: Hinek A, Jain S, Taylor G, Nykanen D, Chitayat D. 2008. High copper levels and increased elastolysis in a patient with cutis marmorata teleangiectasia congenita. Am J Med Genet Part A 146A:2520–2527.

Abstract

Cutis marmorata telangiectatica congenita (CMTC) is a rare cutaneous vascular disease presenting at birth with levido reticularis, phlebectasia, and telangiectasia, often accompanied by skin ulcerations. Extra-dermal vascular anomalies can be also detected in 30–70% of described cases. The pathomechanism responsible for development of these phenotypic changes is not well understood. Here, we report on a 16-month-old boy with CMTC, generalized vascular abnormalities and severe, nitric oxide sensitive, pulmonary hypertension associating with markedly elevated level of blood copper. Results of laboratory investigations indicated that primary cultures (passage one) of dermal fibroblasts derived from this patient were capable of normal synthesis of tropoelastin, but their net deposition of mature elastic fibers was significantly diminished as compared with cultures of normal fibroblasts. Because the low net deposition of elastin was reversed when 1 mg/ml of α1-antitrypsin was added to the media, we conclude that heightened elastolysis by endogenous serine proteinase's is responsible for the low net elastogenesis by CMTC fibroblasts. Since simultaneous addition of 30 µM CuSO4 and 1 mg/ml α1-antitrypsin abolished the beneficial effect of this serine proteinase's inhibitor, we concluded that this may be due to copper-dependent inactivation of α1-antitrypsin. Our data suggest that a high level of free copper may constitute a major triggering factor contributing to the development of the CMTC phenotype. © 2008 Wiley-Liss, Inc.

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