Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy

Anil K. Agarwal, Vinaya Simha, Elif Arioglu Oral, Stephanie A. Moran, Phillip Gorden, Stephen O'Rahilly, Zohra Zaidi, Figen Gurakan, Silva A. Arslanian, Aharon Klar, Alyne Ricker, Neil H. White, Lutz Bindl, Karen Herbst, Kurt Kennel, Shailesh B. Patel, Lihadh Al-Gazali, Abhimanyu Garg

Research output: Contribution to journalArticlepeer-review

205 Citations (Scopus)


Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Recently, mutations in 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2) and Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) genes were reported in pedigrees linked to chromosomes 9q34 and 11q13, respectively. There are limited data regarding phenotypic differences between the various subtypes of CGL. Furthermore, whether there are additional loci for CGL remains unknown. Therefore, we genotyped 45 pedigrees with CGL for AGPAT2 and BSCL2 loci and compared the phenotypes in the various subtypes. Twenty-six pedigrees harbored mutations, including seven novel variants, in the AGPAT2 gene, and 11 pedigrees harbored mutations in the BSCL2 gene, including five novel variants. Eight pedigrees had no substantial alterations in either gene. Of these, three informative pedigrees showed no linkage to markers spanning the AGPAT2 and BSCL2 loci, and in six of the affected subjects, the transcripts of AGPAT2 and BSCL2 were normal. All subtypes of CGL showed high prevalence of diabetes, hypertriglyceridemia, and acanthosis nigricans. However, patients with BSCL2 mutations had lower serum leptin levels, an earlier onset of diabetes, and higher prevalence of mild mental retardation compared with other subtypes. We conclude that besides AGPAT2 and BSCL2, there may be additional loci for CGL. The genetic heterogeneity in CGL patients is accompanied by phenotypic heterogeneity.

Original languageEnglish
Pages (from-to)4840-4847
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number10
Publication statusPublished - Oct 2003

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


Dive into the research topics of 'Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy'. Together they form a unique fingerprint.

Cite this