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General Information
Name
lipodystrophy, congenital generalized, type 2
FlyBase ID
FBhh0000447
Overview

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 OMIM: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]

Disease Summary Information
Parent Disease Summary: lipodystrophy, congenital generalized
Symptoms and phenotype

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 OMIM:269700; 2017.07.10]

Specific Disease Summary: lipodystrophy, congenital generalized, type 2
OMIM report

[LIPODYSTROPHY, CONGENITAL GENERALIZED, TYPE 2; CGL2](https://omim.org/entry/269700)

Human gene(s) implicated

[BSCL2 GENE; BSCL2](https://omim.org/entry/606158)

Symptoms and phenotype

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 OMIM:269700; 2016.11.23]

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]

Genetics

Congenital generalized lipodystrophy type 2 (CGL2) is caused by homozygous or compound heterozygous mutation in the gene encoding seipin (BSCL2). [from OMIM:269700; 2016.11.23]

Cellular phenotype and pathology

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]

Molecular information

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 OMIM:606158; 2016.11.23]

External links
Disease synonyms
Berardinelli-Seip congenital generalized lipodystrophy type 2
Berardinelli-Seip congenital lipodystrophy type 2
Berardinelli-Seip syndrome
CGL2
congenital generalized lipodystrophy
congenital generalized lipodystrophy, type 2
lipodystrophy, Berardinelli-Seip congenital, type 2
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    Seipin (Seipin) encodes a transmembrane protein with roles in ER calcium homeostasis and lipid storage. [Date last reviewed: 2019-03-14]
    Molecular function (GO)
      Gene Groups / Pathways
        Comments on ortholog(s)

        Ortholog of human BSCL2 gene (1 Drosophila to 1 human). Dmel\Seipin shares 31% identity and 51% similarity with human BSCL2.

        Orthologs and Alignments from DRSC
        DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
        Other Genes Used: Viral, Bacterial, Synthetic (0)
          Summary of Physical Interactions (11 groups)
          protein-protein
          Interacting group
          Assay
          References
          anti tag coimmunoprecipitation, anti tag western blot, electron microscopy
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          split luciferase complementation
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting
          anti tag coimmunoprecipitation, peptide massfingerprinting, western blot
          anti tag coimmunoprecipitation, peptide massfingerprinting
          Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
          Models Based on Experimental Evidence ( 2 )
          Modifiers Based on Experimental Evidence ( 1 )
          Allele
          Disease
          Interaction
          References
          is ameliorated by mdyQX25
          is ameliorated by Pcyt116919
          is ameliorated by CdsEY08412
          is exacerbated by mdyQX25
          is exacerbated by Cds1
          is exacerbated by mdyEY07280
          is ameliorated by SCAPEY06708
          is exacerbated by minoEY00734
          is ameliorated by LpinGD14004
          is exacerbated by CdsNIG.7962R
          is ameliorated by mdyEY07280
          Alleles Representing Disease-Implicated Variants
          Genetic Tools, Stocks and Reagents
          Sources of Stocks
          Contact lab of origin for a reagent not available from a public stock center.
          Bloomington Stock Center Disease Page
          Selected mammalian transgenes
          Allele
          Transgene
          Publicly Available Stocks
          Selected Drosophila transgenes
          Allele
          Transgene
          Publicly Available Stocks
          RNAi constructs available
          Allele
          Transgene
          Publicly Available Stocks
          Selected Drosophila classical alleles
          Allele
          Allele class
          Mutagen
          Publicly Available Stocks
          amorphic allele - molecular evidence
          I-SceI
          References (9)