Prevalence of mutations in AGPAT2 among human lipodystrophies.
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.
Magré
Jocelyne
J
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
Delépine
Marc
M
Van Maldergem
Lionel
L
Robert
Jean-Jacques
JJ
Maassen
J Antonie
JA
Meier
Muriel
M
Panz
Vanessa R
VR
Kim
Chong Ae
CA
Tubiana-Rufi
Nadia
N
Czernichow
Paul
P
Seemanova
Eva
E
Buchanan
Charles R
CR
Lacombe
Didier
D
Vigouroux
Corinne
C
Lascols
Olivier
O
Kahn
C Ronald
CR
Capeau
Jacqueline
J
Lathrop
Mark
M
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
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