Type A Insulin Resistance Syndrome Revealing a Novel Lamin A Mutation
Jacques Young 1 ,
Louise Morbois-Trabut 2 ,
Béatrice Couzinet 1 ,
Olivier Lascols 2 3 ,
Elisabeth Dion 4 ,
Véronique Béréziat 2 ,
Bruno Fève 1 ,
Isabelle Richard 5 ,
Jacqueline Capeau 2 ,
Philippe Chanson 1 and
Corinne Vigouroux 2
1 Endocrinology and Reproductive Diseases Department, Assistance Publique-Hôpitaux de Paris, and INSERM U.693, Bicêtre Hospital,
Le Kremlin-Bicêtre, Paris XI University, Paris, France
2 INSERM U680, Saint-Antoine Faculty of Medicine, Pierre and Marie Curie University, Paris, France
3 Molecular Biology Department, Saint-Antoine Hospital, Paris, France
4 Radiology Department, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
5 Généthon CNRS UMR8115, Evry, France
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.
DEXA, dual-energy X-ray absorptiometry
ERK, extracellular regulated kinase
FPLD, familial partial lipodystrophy of the Dunnigan type
IRβ, insulin receptor β subunit
IRS-1, insulin receptor substrate-1
PCOS, polycystic ovary syndrome
PKB, protein kinase B
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.
DIABETES...

Type A Insulin Resistance Syndrome Revealing a Novel Lamin A Mutation

10.2337/diabetes.54.6.1873