title: Prevalence of mutations in AGPAT2 among human lipodystrophies.
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.
authors.affiliation: INSERM U.402, Saint-Antoine Faculty of Medicine, University of Pierre and Marie Curie, 27 rue Chaligny, 75571 Paris Cedex, France. magre@st-antoine.inserm.fr
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Magré
authors.forename: Marc
authors.initials: M
authors.lastname: Delépine
authors.forename: Lionel
authors.initials: L
authors.lastname: Van Maldergem
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Robert
authors.forename: J Antonie
authors.initials: JA
authors.lastname: Maassen
authors.forename: Muriel
authors.initials: M
authors.lastname: Meier
authors.forename: Vanessa R
authors.initials: VR
authors.lastname: Panz
authors.forename: Chong Ae
authors.initials: CA
authors.lastname: Kim
authors.forename: Nadia
authors.initials: N
authors.lastname: Tubiana-Rufi
authors.forename: Paul
authors.initials: P
authors.lastname: Czernichow
authors.forename: Eva
authors.initials: E
authors.lastname: Seemanova
authors.forename: Charles R
authors.initials: CR
authors.lastname: Buchanan
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Corinne
authors.initials: C
authors.lastname: Vigouroux
authors.forename: Olivier
authors.initials: O
authors.lastname: Lascols
authors.forename: C Ronald
authors.initials: CR
authors.lastname: Kahn
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D000217:Acyltransferases / Q000235:genetics*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D002899:Chromosomes, Human, Pair 9; D017931:DNA Primers; D005260:Female; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D008060:Lipodystrophy / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: C432679:BSCL2 protein, human; D017931:DNA Primers; D044388:GTP-Binding Protein gamma Subunits; D000217:Acyltransferases; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D020962:Heterotrimeric GTP-Binding Proteins