This report describes lipodystrophy, congenital generalized, type 2 (CGL2), also known as Berardinelli-Seip congenital lipodystrophy type 2; CGL2 exhibits autosomal recessive inheritance. The gene implicated in this disease is BSCL2, which encodes Seipen, a multi-pass transmembrane protein that localizes to the endoplasmic reticulum and is predicted to function in lipid droplet formation and/or metabolism. BSCL2 has been implicated in multiple diseases (see MIM:606158; see also FBhh0000451). There is a single orthologous gene in Drosophila, Seipin, for which an amorphic allele and multiple RNAi targeting constructs have been generated.
UAS constructs of the human gene Hsap\BSCL2 have been introduced into flies, including a disease variant associated with spastic paraplegia 17 (FBhh0000451). Heterologous rescue (functional complementation) has been demonstrated.
Larvae homozygous for an amorphic mutation of Seipin exhibit reduced lipid storage in fat bodies and ectopic lipid droplets in the salivary glands. Genetic interactions of candidate genes have been assessed based on modification of this phenotype. Multiple physical interactions have been reported; see below and in the Seipin gene report.
[updated Jul. 2017 by FlyBase; FBrf0222196]
Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes (Garg, 2004; pubmed:15028826). [from MIM:269700; 2017.07.10]
[LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 2; CGL2](https://omim.org/entry/269700)
[BSCL2 GENE; BSCL2](https://omim.org/entry/606158)
Affected individuals develop insulin resistance and approximately 25%-35% develop diabetes mellitus between ages 15 and 20 years. Hepatomegaly secondary to hepatic steatosis and skeletal muscle hypertrophy occur in all affected individuals. Hypertrophic cardiomyopathy is reported in 20%-25% of affected individuals and is a significant cause of morbidity from cardiac failure and early mortality. [from Gene Reviews, Berardinelli-Seip Congenital Lipodystrophy; 2016.11.23]
Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is an autosomal recessive disorder characterized by near absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes (Garg, 2004; pubmed:15028826). [from MIM:269700; 2016.11.23]
Congenital generalized lipodystrophy type 2 (CGL2) is caused by homozygous or compound heterozygous mutation in the gene encoding seipin (BSCL2). [from MIM:269700; 2016.11.23]
Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscle and liver. [from Gene Reviews, Berardinelli-Seip Congenital Lipodystrophy; 2016.11.23]
BSCL2, or seipin, is an endoplasmic reticulum (ER)-resident protein that is induced in late stages of preadipocyte differentiation and is predicted to function in lipid droplet formation and/or metabolism (summary by Cui et al., 2011; pubmed:21551454). [from MIM:606158; 2016.11.23]
One to one: 1 human to 1 Drosophila.
Ortholog of human BSCL2 gene (1 Drosophila to 1 human). Dmel\Seipin shares 31% identity and 51% similarity with human BSCL2.
