Phenotypic heterogeneity in biochemical parameters correlates with mutations in AGPAT2 or Seipin genes among Berardinelli-Seip congenital lipodystrophy patients.

The Berardinelli-Seip congenital lipodystrophy (BSCL) syndrome is characterized by a near-total congenital absence of fat and predisposition to develop diabetes mellitus. We have previously reported that 22 patients from 16 consanguineous pedigrees living in the northeastern region of Brazil had a homozygous 669insA mutation in the Seipin gene (BSCL2 locus), while all of the 10 investigated subjects from the southeastern region were homozygous for a 1036 bp deletion in the AGPAT2 gene (BSCL1 locus). In this study, we compared the serum insulin and insulin resistance (HOMA), leptin, triglyceride and fasting glucose levels in individuals of these two genetically distinct clusters of BSCL subjects. The onset of diabetes was also estimated. The fasting glucose and triglyceride levels were not significantly different in these groups. Significant differences were detected for leptin, insulin and insulin resistance. BSCL1 patients presented lower serum leptin levels compared to BSCL2 patients. BSCL2 subjects had earlier onset of diabetes and higher insulin levels. In agreement, BSCL2 patients were more insulin resistant, as detected by HOMA. These results indicate phenotypic heterogeneity between BSCL1 and BSCL2 Brazilian subjects.