Prevalence of Mutations in AGPAT2 Among Human Lipodystrophies
- Jocelyne Magré1,
- Marc Delépine2,
- Lionel Van Maldergem3,
- Jean-Jacques Robert4,
- J. Antonie Maassen5,
- Muriel Meier1,
- Vanessa R. Panz6,
- Chong Ae Kim7,
- Nadia Tubiana-Rufi8,
- Paul Czernichow8,
- Eva Seemanova9,
- Charles R. Buchanan10,
- Didier Lacombe11,
- Corinne Vigouroux1,
- Olivier Lascols1,
- C. Ronald Kahn12,
- Jacqueline Capeau1 and
- Mark Lathrop2
- 1INSERM U.402, Saint-Antoine Faculty of Medicine, University of Pierre and Marie Curie, Paris, France
- 2National Center of Genotyping, Evry, France
- 3Center of Human Genetics, Institute of Pathology and Genetics, Loverval, Belgium
- 4Department of Pediatric Diabetology, Necker Hospital, Paris, France
- 5Sylvius Laboratory, University of Leiden Medical Center, Leiden, the Netherlands
- 6Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa
- 7Department of Pediatrics, da Crianca Institute, University of Sao Paulo, Sao Paulo, Brazil
- 8Department of Pediatric Endocrinology, Robert Debré Hospital, Paris, France
- 9Department of Clinical Genetics, Charles University, Prague, Czech Republic
- 10Department of Child Health, King’s College Hospital, London, U.K
- 11Department of Medical Genetics, Pellegrin-Enfants Hospital, Bordeaux, France
- 12Joslin Diabetes Center, Harvard University, Boston, Massachusetts
Abstract
Berardinelli-Seip congenital lipodystrophy (BSCL) is a heterogeneous genetic disease characterized by near absence of adipose tissue and severe insulin resistance. We have previously identified mutations in the seipin gene in a subset of our patients’ cohort. Recently, disease-causing mutations in AGPAT2 have been reported in BSCL patients. In this study, we have performed mutation screening in AGPAT2 and the related AGPAT1 in patients with BSCL or other forms of lipodystrophy who have no detectable mutation in the seipin gene. We found 38 BSCL patients from 30 families with mutations in AGPAT2. Three of the known mutations were frequently found in our families. Of the eight new alterations, six are null mutations and two are missense mutations (Glu172Lys and Ala238Gly). All the patients harboring AGPAT2 mutations presented with typical features of BSCL. We did not find mutations in patients with other forms of lipodystrophies, including the syndromes of Lawrence, Dunnigan, and Barraquer-Simons, or with type A insulin resistance. In conclusion, mutations in the seipin gene and AGPAT2 are confined to the BSCL phenotype. Because we found mutations in 92 of the 94 BSCL patients studied, the seipin gene and AGPAT2 are the two major genes involved in the etiology of BSCL.
Footnotes
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Address correspondence and reprint requests to Jocelyne Magré, INSERM U.402, Faculté de Médecine Saint-Antoine, 27 rue Chaligny, 75571 Paris Cedex, France. E-mail: magre{at}st-antoine.inserm.fr.
Received for publication 19 December 2002 and accepted 18 February 2003.
BSCL, Berardinelli-Seip congenital lipodystrophy; FPLD, familial partial lipodystrophy; LPA, lysophosphatidic acid.
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