Type A Insulin Resistance Syndrome Revealing a Novel Lamin A Mutation

  1. Jacques Young1,
  2. Louise Morbois-Trabut2,
  3. Béatrice Couzinet1,
  4. Olivier Lascols23,
  5. Elisabeth Dion4,
  6. Véronique Béréziat2,
  7. Bruno Fève1,
  8. Isabelle Richard5,
  9. Jacqueline Capeau2,
  10. Philippe Chanson1 and
  11. Corinne Vigouroux2
  1. 1Endocrinology and Reproductive Diseases Department, Assistance Publique-Hôpitaux de Paris, and INSERM U.693, Bicêtre Hospital, Le Kremlin-Bicêtre, Paris XI University, Paris, France
  2. 2INSERM U680, Saint-Antoine Faculty of Medicine, Pierre and Marie Curie University, Paris, France
  3. 3Molecular Biology Department, Saint-Antoine Hospital, Paris, France
  4. 4Radiology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
  5. 5Généthon CNRS UMR8115, Evry, France
  1. Address correspondence and reprint requests to Corinne Vigouroux, Saint-Antoine Faculty of Medicine, INSERM U680, 27 rue Chaligny, 75 571 Paris Cedex 12, France. E-mail: vigouroux{at}st-antoine.inserm.fr

Abstract

Particular forms of polycystic ovary syndrome with severe hyperandrogenism, acanthosis nigricans, and marked insulin resistance, defining the type A insulin resistance syndrome, are due to insulin receptor gene mutations. However, the majority of affected individuals do not have such mutation, arguing for the genetic heterogeneity of this syndrome. The familial partial lipodystrophy of the Dunnigan type, one of the diseases due to mutations in the lamin A/C (LMNA) gene, is characterized by a lipodystrophic phenotype and shares some clinical and metabolic features with the type A syndrome. We describe here the case of a nonobese 24-year-old woman affected with type A syndrome without clinical lipodystrophy. We linked this phenotype to a novel heterozygous missense mutation in the LMNA, predicting a G602S amino acid substitution in lamin A. This mutation cosegregated with impaired glucose tolerance, insulin resistance, and acanthosis nigricans in the absence of clinical lipodystrophy in the family. The skin fibroblasts from the proband exhibited nuclear alterations similar to those described in other laminopathies, and showed several defects in the insulin transduction pathway. This study further extends the vast range of diseases linked to LMNA mutations and identifies another genetic cause for the type A insulin resistance syndrome.

Footnotes

  • Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted February 21, 2005.
    • Received June 25, 2004.
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