Identification of a Novel deletion Mutation in AGPAT2 Gene Associated with Congenital Generalized LiPodystrophy Type 1

Abstract

Background: Congenital generalized lipodystrophy (CGL) also known as BerardinelliSeip Congenital Lipodystrophy (BSCL) is rare autosomal recessive disorder caused by mutation in AGPAT2, BSCL2, CAV1, and PTRF genes characterized by loss of adipose tissues from birth or early infancy, acanthosis nigricans, diabetes mellitus, muscular hypertrophy, hepatomegaly and hypertriglyceridemia. There are four subclinical phenotypes of CGL (CGL1-4) and mutations in four genes AGPAT2, BSCL2, CAV1 and PTRF have been assigned to each type respectively. Methods: DNA was extracted from ten blood samples collected from the members of the AY family. Microarray technique was used to detect the suspected region that include the candidate gene then all the coding exons including splice junctions of AGPAT2 gene was PCR amplified and sequenced directly using an automated DNA sequencer ABI3730. In a second family clinically diagnosed as CGL all the coding exons including splice junctions of AGPAT2, BSCL2, CAV1 and PTRF genes were PCR amplified and sequenced. The mutation detected in the study was screened by Sanger Sequencing in 100 normal controls. Results: Sequence analysis of AY family revealed a novel deletion mutation (delG 662) in exon 6 of AGPAT2 gene causing a frame shift and premature termination codon. The second family (CE) does not show any mutation that may cause CGL. The 100 controls were negative for the AGPAT2 variant. Conclusion: Mutation identified here in AGPAT2 gene causing congenital generalized lipodystrophy is the first report in Palestinian population. The patients exhibited characteristic features of generalized lipodystrophy, acanthosis nigricans, hypertriglyceridemia, diabetes mellitus and hypertrophic cardiomyopathy. . Keywords: Congenital generalized lipodystrophy, Deletion mutation and AGPAT2