AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34.
Congenital generalized lipodystrophy is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes. We report several different mutations of the gene (AGPAT2) encoding 1-acylglycerol-3-phosphate O-acyltransferase 2 in 20 affected individuals from 11 pedigrees of diverse ethnicities showing linkage to chromosome 9q34. The AGPAT2 enzyme catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, a key intermediate in the biosynthesis of triacylglycerol and glycerophospholipids. AGPAT2 mRNA is highly expressed in adipose tissue. We conclude that mutations in AGPAT2 may cause congenital generalized lipodystrophy by inhibiting triacylglycerol synthesis and storage in adipocytes.
Agarwal
Anil K
AK
Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390, USA.
Arioglu
Elif
E
De Almeida
Salome
S
Akkoc
Nurullah
N
Taylor
Simeon I
SI
Bowcock
Anne M
AM
Barnes
Robert I
RI
Garg
Abhimanyu
A
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D000217:Acyltransferases / Q000235:genetics*; D000273:Adipose Tissue / Q000201:enzymology; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D008060:Lipodystrophy / Q000151:congenital / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis
D012333:RNA, Messenger; D014280:Triglycerides; D000217:Acyltransferases; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase