Identification of a novel nonsense mutation and a missense substitution in the AGPAT2 gene causing congenital generalized lipodystrophy type 1

Amirreza Haghighi,Maryam Razzaghy-Azar,Ali Talea,Mahnaz Sadeghian,Sian Ellard,Alireza Haghighi

doi:10.1016/j.ejmg.2012.07.011

Abstract

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disease characterized by the generalized scant of adipose tissue. CGL type 1 is caused by mutations in gene encoding 1-acylglycerol-3-phosphate O-acyltransferase-2 (AGPAT2). A clinical and molecular genetic investigation was performed in affected and unaffected members of two families with CGL type 1. The AGPAT2 coding region was sequenced in index cases of the two families. The presence of the identified mutations in relevant parents was tested. We identified a novel nonsense mutation (c.685G>T, p.Glu229*) and a missense substitution (c.514G>A, p.Glu172Lys). The unaffected parents in both families were heterozygous carrier of the relevant mutation. The results expand genotype–phenotype spectrum in CGL1 and will have applications in prenatal and early diagnosis of the disease. This is the first report of Persian families identified with AGPAT2 mutations.

Highlights

Congenital generalized lipodystrophy (CGL) is a rare metabolic disease, transmitted in an autosomal recessive mode
Studies indicated that CGL increases the risk of development of type 2 diabetes mellitus and cardiovascular diseases [6,7]
We investigated clinical features of the first families with congenital generalized lipodystrophy in Persian population and identified the disease causing acylglycerol-3phosphate O-acyltransferase-2 (AGPAT2) mutations in these two unrelated cases

Summary

Introduction

Congenital generalized lipodystrophy (CGL) is a rare metabolic disease, transmitted in an autosomal recessive mode. The worldwide prevalence of CGL has been estimated at one in 10 million [1]. Rajab et al reported a significantly higher incidence of one in 25,000 births in Oman [2]. The disease is characterized by a near total loss of adipose tissue throughout the body from birth, resulting in a marked and generalized muscular appearance [3]. Studies indicated that CGL increases the risk of development of type 2 diabetes mellitus and cardiovascular diseases [6,7]. Mortality in CGL is mainly due to liver, kidney and heart impairment [8]. Haghighi). 1 The first two authors contributed to this work. 2 These authors contributed to this work

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