CGL
MCID: CNG012
MIFTS: 65

Congenital Generalized Lipodystrophy (CGL)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Immune diseases, Metabolic diseases, Muscle diseases, Rare diseases, Skin diseases

Aliases & Classifications for Congenital Generalized Lipodystrophy

MalaCards integrated aliases for Congenital Generalized Lipodystrophy:

Name: Congenital Generalized Lipodystrophy 12 20 43 58 36 29 6 15 17
Berardinelli-Seip Congenital Lipodystrophy 20 43 58
Berardinelli-Seip Syndrome 20 43 58
Brunzell Syndrome 20 43 6
Bscl 20 43 58
Lipodystrophy, Congenital Generalized 43 54
Generalized Lipodystrophy 43 29
Lipoatrophic Diabetes 20 58
Congenital Generalized Lipodystrophy Type 2 70
Lipodystrophy, Generalized, Congenital 39
Familial Partial Lipodystrophy, Type 2 70
Generalized Congenital Lipodystrophy 20
Familial Generalized Lipodystrophy 70
Lipoatrophic Diabetes Mellitus 70
Beradinelli-Seip Syndrome 20
Total Lipodystrophy 43
Seip Syndrome 43
Gcl 20
Cgl 58

Characteristics:

Orphanet epidemiological data:

58
congenital generalized lipodystrophy
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: Neonatal;

Classifications:

Orphanet: 58  
Rare skin diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Congenital Generalized Lipodystrophy

MedlinePlus Genetics : 43 Congenital generalized lipodystrophy (also called Berardinelli-Seip congenital lipodystrophy) is a rare condition characterized by an almost total lack of fatty (adipose) tissue in the body and a very muscular appearance. Adipose tissue is found in many parts of the body, including beneath the skin and surrounding the internal organs. It stores fat for energy and also provides cushioning. Congenital generalized lipodystrophy is part of a group of related disorders known as lipodystrophies, which are all characterized by a loss of adipose tissue. A shortage of adipose tissue leads to the storage of fat elsewhere in the body, such as in the liver and muscles, which causes serious health problems.The signs and symptoms of congenital generalized lipodystrophy are usually apparent from birth or early childhood. One of the most common features is insulin resistance, a condition in which the body's tissues are unable to recognize insulin, a hormone that normally helps to regulate blood sugar levels. Insulin resistance may develop into a more serious disease called diabetes mellitus. Most affected individuals also have high levels of fats called triglycerides circulating in the bloodstream (hypertriglyceridemia), which can lead to the development of small yellow deposits of fat under the skin called eruptive xanthomas and inflammation of the pancreas (pancreatitis). Additionally, congenital generalized lipodystrophy causes an abnormal buildup of fats in the liver (hepatic steatosis), which can result in an enlarged liver (hepatomegaly) and liver failure. Some affected individuals develop a form of heart disease called hypertrophic cardiomyopathy, which can lead to heart failure and an abnormal heart rhythm (arrhythmia) that can cause sudden death.People with congenital generalized lipodystrophy have a distinctive physical appearance. They appear very muscular because they have an almost complete absence of adipose tissue and an overgrowth of muscle tissue. A lack of adipose tissue under the skin also makes the veins appear prominent. Affected individuals tend to have prominent bones above the eyes (orbital ridges), large hands and feet, and a prominent belly button (umbilicus). Affected females may have an enlarged clitoris (clitoromegaly), an increased amount of body hair (hirsutism), irregular menstrual periods, and multiple cysts on the ovaries, which may be related to hormonal changes. Many people with this disorder develop acanthosis nigricans, a skin condition related to high levels of insulin in the bloodstream. Acanthosis nigricans causes the skin in body folds and creases to become thick, dark, and velvety.Researchers have described four types of congenital generalized lipodystrophy, which are distinguished by their genetic cause. The types also have some differences in their typical signs and symptoms. For example, in addition to the features described above, some people with congenital generalized lipodystrophy type 1 develop cysts in the long bones of the arms and legs after puberty. Type 2 can be associated with intellectual disability, which is usually mild to moderate. Type 3 appears to cause poor growth and short stature, along with other health problems. Type 4 is associated with muscle weakness, delayed development, joint abnormalities, a narrowing of the lower part of the stomach (pyloric stenosis), and severe arrhythmia that can lead to sudden death.

MalaCards based summary : Congenital Generalized Lipodystrophy, also known as berardinelli-seip congenital lipodystrophy, is related to lipodystrophy, congenital generalized, type 4 and lipodystrophy, congenital generalized, type 3, and has symptoms including myalgia An important gene associated with Congenital Generalized Lipodystrophy is AGPAT2 (1-Acylglycerol-3-Phosphate O-Acyltransferase 2), and among its related pathways/superpathways are Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. and Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha). The drugs Propoxycaine and Pharmaceutical Solutions have been mentioned in the context of this disorder. Affiliated tissues include heart, liver and skin, and related phenotypes are hepatomegaly and lipodystrophy

Disease Ontology : 12 A lipodystrophy that is characterized by extreme scarcity of subcutaneous fat, muscular hypertrophy, fatty liver, hypertriglyceremia and metabolic complications including insulin resistance.

GARD : 20 Congenital generalized lipodystrophy is a rare disease characterized by a generalized lack of fat (adipose tissue ) in the body. It is part of a group of diseases known as lipodystrophies. Signs and symptoms are noticed from birth (congenital) or early childhood and include high levels of fats (triglycerides) in the blood (hypertriglyceridemia) and insulin resistance (in which the body tissues are unable to respond to the hormone insulin that helps to regulate blood sugar levels) resulting in diabetes mellitus, abnormal accumulation of fat in the liver (liver steatosis) and the accumulation of fat in the heart causing a thickening of the heart muscle ( hypertrophic cardiomyopathy ), which can lead to a heart that does not work well (heart failure) and sudden death. Due to the almost total absence of fatty tissue and excessive growth of muscle tissue, the patients appear very muscular and have visible and prominent veins. They also have dark and thick skin in the body folds ( acanthosis nigricans ). There are 4 types of the disease that are distinguished by the altered ( mutated ) genes and by some additional characteristic symptoms. People with type 1, caused by mutations in the AGPAT2 gene, may have cysts in the long bones of the arms and the legs after puberty. In type 2, which is caused by mutations in the BSCL2 gene, there may be intellectual disability. In type 3, caused by mutations in the CAV1 gene, affected people may have short stature and growth delay. Type 4, caused by mutations in the CAVIN1 gene, is associated with muscle weakness, developmental delay, joint anomalies, narrowing of the lower part of the stomach (pyloric stenosis), and severe heart arrhythmia that can lead to sudden death. The inheritance of Berardinelli-Seip congenital lipodystrophy is autosomal recessive. Treatment consists on a fat restricted diet and diabetes control, and may also include leptin administration.

KEGG : 36 Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disease characterized by near total absence of adipose tissue from birth. Several metabolic alterations in carbohydrate (diabetes mellitus) and lipid metabolism and involvement of heart, bone and ovaries are also observed in this disease. Patients typically have low serum levels of leptin and adiponectin. Several genes were studied to identify the molecular alteration responsible for CGL, which have been found to contribute to lipid droplet formation in adipocytes.

Wikipedia : 73 Congenital generalized lipodystrophy (also known as Berardinelli-Seip lipodystrophy) is an extremely... more...

Related Diseases for Congenital Generalized Lipodystrophy

Diseases in the Acquired Generalized Lipodystrophy family:

Lipodystrophy, Congenital Generalized, Type 2 Lipodystrophy, Congenital Generalized, Type 1
Lipodystrophy, Congenital Generalized, Type 3 Lipodystrophy, Congenital Generalized, Type 4
Congenital Generalized Lipodystrophy

Diseases related to Congenital Generalized Lipodystrophy via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 319)
# Related Disease Score Top Affiliating Genes
1 lipodystrophy, congenital generalized, type 4 33.5 CAVIN1 CAV1 BSCL2 AGPAT2
2 lipodystrophy, congenital generalized, type 3 33.3 LPIN1 CAVIN1 CAV1 BSCL2 AGPAT2
3 lipodystrophy, congenital generalized, type 1 33.2 LPIN1 LEP GZMB GPAT3 CAVIN1 BSCL2
4 lipodystrophy, familial partial, type 2 32.9 ZMPSTE24 PPARG LMNA LEP INS CIDEC
5 lipodystrophy, congenital generalized, type 2 32.7 PPARG LPIN1 LMNA LEP INS HNRNPUL2-BSCL2
6 berardinelli-seip congenital lipodystrophy 32.5 LEPQTL1 LEP HNRNPUL2-BSCL2 CAVIN1 CAV1 BSCL2
7 mandibuloacral dysplasia with type a lipodystrophy 32.4 ZMPSTE24 LMNA
8 acquired generalized lipodystrophy 32.4 ZMPSTE24 LMNA LEP CIDEC CAVIN1 BSCL2
9 mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome 31.9 ZMPSTE24 PPARG LPIN1 LMNA LEP INS
10 complete generalized lipodystrophy 31.7 ZMPSTE24 PPARG LPIN1 LMNA LEP INS
11 acanthosis nigricans 31.5 PPARG LMNA LEP INSR INS ADIPOQ
12 non-alcoholic fatty liver disease 31.2 PPARG LEP INSR INS ADIPOQ
13 neuronopathy, distal hereditary motor, type vc 31.2 HNRNPUL2-BSCL2 BSCL2
14 spastic paraplegia 17 31.1 HNRNPUL2-BSCL2 BSCL2
15 fatty liver disease 31.1 PPARG LEP INSR INS ADIPOQ
16 hyperinsulinism 31.1 PPARG LEPQTL1 LEP INSR INS ADIPOQ
17 lipid metabolism disorder 31.0 PPARG LMNA LEP INSR INS ADIPOQ
18 hyperglycemia 30.9 PPARG LEP INSR INS ADIPOQ
19 acquired lipodystrophy 30.7 CAV1 BSCL2
20 lysosomal storage disease 30.6 PPARG LEP INS ADIPOQ
21 monogenic diabetes 30.6 LMNA INS HNRNPUL2-BSCL2 BSCL2
22 polycystic ovary syndrome 30.6 PPARG LEP INSR INS ADIPOQ
23 hyperandrogenism 30.5 PPARG INSR INS ADIPOQ
24 insulin-like growth factor i 30.5 LEP INSR INS
25 liver disease 30.5 LEP INSR INS FOS ADIPOQ
26 abdominal obesity-metabolic syndrome 1 30.5 PPARG LEP INSR INS ADIPOQ
27 hyperuricemia 30.5 PPARG LEP INS
28 type 2 diabetes mellitus 30.4 PPARG LPIN1 LMNA LEPQTL1 LEP INSR
29 ovarian disease 30.4 PPARG LEP INSR INS ADIPOQ
30 hutchinson-gilford progeria syndrome 30.4 ZMPSTE24 LMNA ADIPOQ
31 glucose intolerance 30.4 PPARG LMNA LEP INSR INS ADIPOQ
32 liver cirrhosis 30.4 PPARG LEP INSR INS CAV1 ADIPOQ
33 leptin deficiency or dysfunction 30.4 PPARG LEP INS ADIPOQ
34 non-alcoholic steatohepatitis 30.3 PPARG INS ADIPOQ
35 familial partial lipodystrophy 30.3 PPARG LMNA LEP INS CIDEC BSCL2
36 body mass index quantitative trait locus 11 30.2 PPARG LPIN1 LMNA LEPQTL1 LEP INSR
37 diabetes mellitus 30.1 PPARG LPIN1 LMNA LEP INSR INS
38 hypertension, essential 30.1 PPARG LEP INSR INS FOS CAV1
39 aredyld 11.6
40 keppen-lubinsky syndrome 11.5
41 krabbe disease 11.3
42 generalized lipodystrophy-associated progeroid syndrome 11.2
43 mandibuloacral dysplasia with type b lipodystrophy 11.0
44 proteasome-associated autoinflammatory syndrome 4 11.0
45 leukemia, chronic myeloid 11.0
46 glutamate-cysteine ligase deficiency 11.0
47 hypertriglyceridemia, familial 10.7
48 autosomal recessive disease 10.7
49 lipedema 10.5 PPARG LEP
50 autism 6 10.5 LEPQTL1 LEP

Graphical network of the top 20 diseases related to Congenital Generalized Lipodystrophy:



Diseases related to Congenital Generalized Lipodystrophy

Symptoms & Phenotypes for Congenital Generalized Lipodystrophy

Human phenotypes related to Congenital Generalized Lipodystrophy:

58 31 (show all 38)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
2 lipodystrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0009125
3 insulin resistance 58 31 hallmark (90%) Very frequent (99-80%) HP:0000855
4 adipose tissue loss 58 31 hallmark (90%) Very frequent (99-80%) HP:0008887
5 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
6 diabetes mellitus 58 31 frequent (33%) Frequent (79-30%) HP:0000819
7 hypertriglyceridemia 58 31 frequent (33%) Frequent (79-30%) HP:0002155
8 hypertrichosis 58 31 frequent (33%) Frequent (79-30%) HP:0000998
9 failure to thrive 58 31 occasional (7.5%) Occasional (29-5%) HP:0001508
10 macroglossia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000158
11 global developmental delay 58 31 occasional (7.5%) Occasional (29-5%) HP:0001263
12 prominent supraorbital ridges 58 31 occasional (7.5%) Occasional (29-5%) HP:0000336
13 mandibular prognathia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000303
14 abnormal facial shape 58 31 occasional (7.5%) Occasional (29-5%) HP:0001999
15 congestive heart failure 58 31 occasional (7.5%) Occasional (29-5%) HP:0001635
16 hepatic steatosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001397
17 low posterior hairline 58 31 occasional (7.5%) Occasional (29-5%) HP:0002162
18 hyperinsulinemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000842
19 cirrhosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001394
20 hypertrophic cardiomyopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001639
21 hypercholesterolemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0003124
22 low anterior hairline 58 31 occasional (7.5%) Occasional (29-5%) HP:0000294
23 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%) HP:0000956
24 bone cyst 58 31 occasional (7.5%) Occasional (29-5%) HP:0012062
25 large hands 58 31 occasional (7.5%) Occasional (29-5%) HP:0001176
26 accelerated skeletal maturation 58 31 occasional (7.5%) Occasional (29-5%) HP:0005616
27 psychomotor retardation 58 31 occasional (7.5%) Occasional (29-5%) HP:0025356
28 long foot 58 31 occasional (7.5%) Occasional (29-5%) HP:0001833
29 clitoral hypertrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008665
30 prominent superficial veins 58 31 occasional (7.5%) Occasional (29-5%) HP:0001015
31 proportionate tall stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0011407
32 increased c-peptide level 58 31 occasional (7.5%) Occasional (29-5%) HP:0030796
33 overgrowth of external genitalia 58 31 occasional (7.5%) Occasional (29-5%) HP:0003247
34 polycystic ovaries 58 31 very rare (1%) Very rare (<4-1%) HP:0000147
35 amenorrhea 58 31 very rare (1%) Very rare (<4-1%) HP:0000141
36 oligomenorrhea 58 31 very rare (1%) Very rare (<4-1%) HP:0000876
37 precocious puberty in females 58 31 very rare (1%) Very rare (<4-1%) HP:0010465
38 skeletal muscle hypertrophy 58 Very frequent (99-80%)

UMLS symptoms related to Congenital Generalized Lipodystrophy:


myalgia

MGI Mouse Phenotypes related to Congenital Generalized Lipodystrophy:

46 (show all 18)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.5 ADIPOQ AGPAT1 AGPAT2 BSCL2 CAV1 CAVIN1
2 adipose tissue MP:0005375 10.45 ADIPOQ AGPAT1 AGPAT2 BSCL2 CAV1 CIDEC
3 growth/size/body region MP:0005378 10.41 ADIPOQ AGPAT1 AGPAT2 BSCL2 CAV1 CAVIN1
4 homeostasis/metabolism MP:0005376 10.41 ADIPOQ AGPAT1 AGPAT2 BSCL2 CAV1 CAVIN1
5 cellular MP:0005384 10.39 ADIPOQ AGPAT1 AGPAT2 BSCL2 CAV1 CAVIN1
6 cardiovascular system MP:0005385 10.37 ADIPOQ AGPAT1 BSCL2 CAV1 CAVIN1 FOS
7 endocrine/exocrine gland MP:0005379 10.34 ADIPOQ AGPAT1 AGPAT2 BSCL2 CAV1 FOS
8 hematopoietic system MP:0005397 10.31 ADIPOQ AGPAT1 AGPAT2 BSCL2 CAV1 CIDEC
9 liver/biliary system MP:0005370 10.25 ADIPOQ AGPAT2 BSCL2 CAV1 CIDEC GPAT3
10 integument MP:0010771 10.21 ADIPOQ AGPAT2 BSCL2 CAV1 CIDEC FOS
11 mortality/aging MP:0010768 10.21 ADIPOQ AGPAT1 AGPAT2 BSCL2 CAV1 CAVIN1
12 immune system MP:0005387 10.2 ADIPOQ AGPAT2 BSCL2 CAV1 FOS INS
13 digestive/alimentary MP:0005381 10.14 AGPAT2 BSCL2 CAV1 INS INSR LEP
14 nervous system MP:0003631 10.1 ADIPOQ AGPAT1 BSCL2 CAV1 CIDEC FOS
15 muscle MP:0005369 10.06 ADIPOQ CAV1 CAVIN1 INS INSR LEP
16 renal/urinary system MP:0005367 9.9 ADIPOQ AGPAT2 BSCL2 CAV1 CAVIN1 INS
17 reproductive system MP:0005389 9.65 AGPAT1 BSCL2 CAV1 FOS INS INSR
18 skeleton MP:0005390 9.36 ADIPOQ AGPAT2 BSCL2 CAV1 FOS INS

Drugs & Therapeutics for Congenital Generalized Lipodystrophy

Drugs for Congenital Generalized Lipodystrophy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Propoxycaine Approved Phase 4 86-43-1
2 Pharmaceutical Solutions Phase 4
3 Anesthetics, Local Phase 4
4 Anesthetics Phase 4
5 Proxymetacaine Phase 4
6
Empagliflozin Approved Phase 3 864070-44-0
7 insulin Phase 3
8 Insulin, Globin Zinc Phase 3
9 Sodium-Glucose Transporter 2 Inhibitors Phase 3
10 Hypoglycemic Agents Phase 3
11 Antibodies Phase 2
12 Immunoglobulins Phase 2

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 A 36-Month, Multicenter, Open Label Phase 4 Study to Evaluate the Immunogenicity of Daily SC Metreleptin Treatment in Patients With Generalized Lipodystrophy Recruiting NCT04026178 Phase 4 Metreleptin
2 Efficacy and Safety of Anesthetic Impregnated Bandage Soft Contact Lens (BSCL) in Pain Management After Photorefractive Keratectomy (PRK). Recruiting NCT04283331 Phase 4 Proparacaine Ophthalmic
3 Double-Blind, Placebo-Controlled Trial of Leptin Replacement Therapy in Patients With Lipodystrophy Completed NCT00896298 Phase 2, Phase 3 Leptin;Placebo
4 A Multicenter, Open-label, Single-arm, Extension Study With Regard to the Safety and Efficacy of Empagliflozin in Patients With Refractory Diabetes Mellitus With Insulin Resistance (EMPIRE-02) Recruiting NCT04221152 Phase 3 Empagliflozin Tablets
5 Compassionate Use of Metreleptin in Previously-Treated Patients With Partial Lipodystrophy Recruiting NCT02262806 Phase 3 Metreleptin
6 Compassionate Use of Metreleptin in Previously-Treated Patients With Generalized Lipodystrophy Active, not recruiting NCT02262832 Phase 3 Metreleptin
7 A Multicenter, Open-label, Single-arm Study With Regard to the Efficacy and Safety of Empagliflozin in Patients With Refractory Diabetes Mellitus With Insulin Resistance Active, not recruiting NCT04018365 Phase 3 Empagliflozin Tablets
8 A Randomized, Double-Blind, Placebo-Controlled Study of REGN4461, a Leptin Receptor Agonist Antibody, in Patients With Generalized Lipodystrophy Active, not recruiting NCT04159415 Phase 2 Placebo;Low-Dose REGN4461;High-dose REGN4461
9 Lipodystrophy Connect Patient Registry Completed NCT02577952
10 Osse Registry for Patients With Lipodystrophy Run by the European Consortium of Lipodystrophies (ECLip) Recruiting NCT03553420
11 Expanded Access to REGN4461 for Patients With 1) Generalized Lipodystrophy, 2) Partial Lipodystrophy or 3) Monogenic Obesity Due to LEP or LEPR Loss of Function Available NCT04710056 REGN4461

Search NIH Clinical Center for Congenital Generalized Lipodystrophy

Genetic Tests for Congenital Generalized Lipodystrophy

Genetic tests related to Congenital Generalized Lipodystrophy:

# Genetic test Affiliating Genes
1 Congenital Generalized Lipodystrophy (disease) 29
2 Generalized Lipodystrophy 29

Anatomical Context for Congenital Generalized Lipodystrophy

MalaCards organs/tissues related to Congenital Generalized Lipodystrophy:

40
Heart, Liver, Skin, Pancreas, Bone, Adipocyte, Skeletal Muscle

Publications for Congenital Generalized Lipodystrophy

Articles related to Congenital Generalized Lipodystrophy:

(show top 50) (show all 355)
# Title Authors PMID Year
1
Severe cardiac phenotype of Berardinelli-Seip congenital lipodystrophy in an infant with homozygous E189X BSCL2 mutation. 6 54 61
19041432 2009
2
Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy. 54 61 6
18211975 2008
3
Novel BSCL2 gene mutation E189X in Chinese congenital generalized lipodystrophy child with early onset diabetes mellitus. 54 6 61
18057387 2007
4
Mutations in the seipin and AGPAT2 genes clustering in consanguineous families with Berardinelli-Seip congenital lipodystrophy from two separate geographical regions of Brazil. 6 54 61
14715872 2004
5
AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34. 6 54 61
11967537 2002
6
Molecular analysis of Berardinelli-Seip congenital lipodystrophy in Oman: evidence for multiple loci. 6 61 54
11916958 2002
7
The lipodystrophy protein seipin is found at endoplasmic reticulum lipid droplet junctions and is important for droplet morphology. 6 54
18093937 2007
8
Mutations in Gng3lg and AGPAT2 in Berardinelli-Seip congenital lipodystrophy and Brunzell syndrome: phenotype variability suggests important modifier effects. 61 6
15181077 2004
9
Gene and phenotype analysis of congenital generalized lipodystrophy in Japanese: a novel homozygous nonsense mutation in seipin gene. 6 61
15126564 2004
10
Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. 6 61
11479539 2001
11
Whole exome sequencing identifies de novo heterozygous CAV1 mutations associated with a novel neonatal onset lipodystrophy syndrome. 6
25898808 2015
12
Cardiomyopathy in congenital complete lipodystrophy. 6
12030893 2002
13
Higher adiponectin levels in patients with Berardinelli-Seip congenital lipodystrophy due to seipin as compared with 1-acylglycerol-3-phosphate-o-acyltransferase-2 deficiency. 61 54
20097706 2010
14
Two Japanese infants with congenital generalized lipodystrophy due to BSCL2 mutations. 61 54
19438831 2009
15
Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli-Seip congenital generalized lipodystrophy syndrome. 61 54
19226263 2009
16
The human lipodystrophy gene product Berardinelli-Seip congenital lipodystrophy 2/seipin plays a key role in adipocyte differentiation. 54 61
19574402 2009
17
Seipin deficiency alters fatty acid Delta9 desaturation and lipid droplet formation in Berardinelli-Seip congenital lipodystrophy. 54 61
19278620 2009
18
Seipinopathy: a novel endoplasmic reticulum stress-associated disease. 61 54
18790819 2009
19
Atypical generalized lipoatrophy and severe insulin resistance due to a heterozygous LMNA p.T10I mutation. 54 61
19169477 2008
20
Novel subtype of congenital generalized lipodystrophy associated with muscular weakness and cervical spine instability. 54 61
18698612 2008
21
Energy balance in congenital generalized lipodystrophy type I. 61 54
18640396 2008
22
Founder effect of the 669insA mutation in BSCL2 gene causing Berardinelli-Seip congenital lipodystrophy in a cluster from Brazil. 54 61
17535271 2007
23
Dental and periodontal alterations in Berardinelli-Seip syndrome. 61 54
17506386 2007
24
Long-term effects of recombinant human insulin-like growth factor I treatment on glucose and lipid metabolism and the growth of a patient with congenital generalized lipodystrophy. 54 61
16902264 2006
25
A regulatory role for 1-acylglycerol-3-phosphate-O-acyltransferase 2 in adipocyte differentiation. 54 61
16495223 2006
26
Diseases of adipose tissue: genetic and acquired lipodystrophies. 61 54
16246048 2005
27
Congenital generalized lipodystrophy in a 4 year old Chinese girl. 61 54
16269843 2005
28
Enzymatic activity of naturally occurring 1-acylglycerol-3-phosphate-O-acyltransferase 2 mutants associated with congenital generalized lipodystrophy. 61 54
15629135 2005
29
[Generalized congenital lipodystrophy: correlation with leptin and other biochemical parameters]. 54 61
17768808 2005
30
Phenotypic heterogeneity in biochemical parameters correlates with mutations in AGPAT2 or Seipin genes among Berardinelli-Seip congenital lipodystrophy patients. 54 61
16435205 2005
31
Congenital generalized lipodystrophy: profile of the disease and gender differences in two siblings. 54 61
15617555 2005
32
Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: baseline characteristics and course during recombinant leptin therapy. 54 61
15240593 2004
33
Genetic basis of congenital generalized lipodystrophy. 54 61
14557833 2004
34
Phenotypic heterogeneity in body fat distribution in patients with congenital generalized lipodystrophy caused by mutations in the AGPAT2 or seipin genes. 54 61
14602785 2003
35
Phenotypic and genetic heterogeneity in congenital generalized lipodystrophy. 54 61
14557463 2003
36
Monogenic forms of insulin resistance: apertures that expose the common metabolic syndrome. 61 54
14516935 2003
37
Prevalence of mutations in AGPAT2 among human lipodystrophies. 61 54
12765973 2003
38
Effect of leptin replacement on intrahepatic and intramyocellular lipid content in patients with generalized lipodystrophy. 61 54
12502655 2003
39
Effect of subcutaneous leptin replacement therapy on bone metabolism in patients with generalized lipodystrophy. 61 54
12414854 2002
40
Serum adiponectin and leptin levels in patients with lipodystrophies. 61 54
11994394 2002
41
Congenital generalized lipodystrophy in a 4-month-old infant. 61 54
11695279 2001
42
Skeletal muscle morphology and exercise response in congenital generalized lipodystrophy. 54 61
11023150 2000
43
Studies of insulin resistance in congenital generalized lipodystrophy. 61 54
8783770 1996
44
Severe islet amyloidosis in congenital generalized lipodystrophy. 54 61
8720529 1996
45
Prevalence of mutations in the insulin receptor gene in subjects with features of the type A syndrome of insulin resistance. 54 61
8288049 1994
46
Clostridial gas gangrene associated with congenital generalized lipodystrophy: report of a case. 54 61
7780235 1994
47
Insulin requirements in lipodystrophic diabetes. 61 54
8281734 1993
48
Trial of insulinlike growth factor I therapy for patients with extreme insulin resistance syndromes. 54 61
8482426 1993
49
Eating behaviour in contrasting adiposity phenotypes: Monogenic obesity and congenital generalized lipodystrophy. 61
33030294 2021
50
Altered acylated ghrelin response to food intake in congenital generalized lipodystrophy. 61
33411809 2021

Variations for Congenital Generalized Lipodystrophy

ClinVar genetic disease variations for Congenital Generalized Lipodystrophy:

6 (show top 50) (show all 179)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CAV1 NM_001753.5(CAV1):c.112G>T (p.Glu38Ter) SNV Pathogenic 8467 rs121434501 GRCh37: 7:116166660-116166660
GRCh38: 7:116526606-116526606
2 AGPAT2 NM_006412.4(AGPAT2):c.683T>C (p.Leu228Pro) SNV Pathogenic 6627 rs104894100 GRCh37: 9:139568358-139568358
GRCh38: 9:136673906-136673906
3 AGPAT2 NM_006412.4(AGPAT2):c.643A>T (p.Lys215Ter) SNV Pathogenic 6629 rs121908925 GRCh37: 9:139569205-139569205
GRCh38: 9:136674753-136674753
4 AGPAT2 NM_006412.4(AGPAT2):c.570C>A (p.Tyr190Ter) SNV Pathogenic 6631 rs121908926 GRCh37: 9:139571055-139571055
GRCh38: 9:136676603-136676603
5 AGPAT2 NM_006412.4(AGPAT2):c.366_588+534del Deletion Pathogenic 6632 GRCh37: 9:139570503-139571539
GRCh38: 9:136676051-136677087
6 CAV1 NM_001753.5(CAV1):c.424C>T (p.Gln142Ter) SNV Pathogenic 209106 rs797045176 GRCh37: 7:116199228-116199228
GRCh38: 7:116559174-116559174
7 CAV1 NM_001753.5(CAV1):c.479_480del (p.Leu159_Phe160insTer) Deletion Pathogenic 208669 rs797044871 GRCh37: 7:116199282-116199283
GRCh38: 7:116559228-116559229
8 AGPAT2 NM_006412.4(AGPAT2):c.406G>A (p.Gly136Arg) SNV Pathogenic 210104 rs797045222 GRCh37: 9:139571499-139571499
GRCh38: 9:136677047-136677047
9 AGPAT2 NM_006412.4(AGPAT2):c.538del (p.Asp180fs) Deletion Pathogenic 372109 rs1057517653 GRCh37: 9:139571087-139571087
GRCh38: 9:136676635-136676635
10 AGPAT2 NM_006412.4(AGPAT2):c.661+2T>G SNV Pathogenic 372110 rs1057517654 GRCh37: 9:139569185-139569185
GRCh38: 9:136674733-136674733
11 AGPAT2 NM_006412.3(AGPAT2):c.(316+1_317-1)_(588+1_589-1)del (p.Leu107AlafsTer279) Deletion Pathogenic 372107 GRCh37:
GRCh38:
12 AGPAT2 NM_006412.4(AGPAT2):c.183-2A>G SNV Pathogenic 372102 rs1057517649 GRCh37: 9:139572010-139572010
GRCh38: 9:136677558-136677558
13 AGPAT2 NM_006412.4(AGPAT2):c.492+1G>A SNV Pathogenic 372106 rs933422777 GRCh37: 9:139571412-139571412
GRCh38: 9:136676960-136676960
14 AGPAT2 NM_006412.4(AGPAT2):c.182+1G>A SNV Pathogenic 372103 rs1057517650 GRCh37: 9:139581627-139581627
GRCh38: 9:136687175-136687175
15 AGPAT2 NM_006412.4(AGPAT2):c.503G>A (p.Trp168Ter) SNV Pathogenic 374338 rs1057518714 GRCh37: 9:139571122-139571122
GRCh38: 9:136676670-136676670
16 AGPAT2 NM_006412.4(AGPAT2):c.513del (p.Glu172fs) Deletion Pathogenic 549711 rs1564290914 GRCh37: 9:139571112-139571112
GRCh38: 9:136676660-136676660
17 AGPAT2 NM_006412.4(AGPAT2):c.622_626del (p.Ser208fs) Deletion Pathogenic 549712 rs1564290079 GRCh37: 9:139569222-139569226
GRCh38: 9:136674770-136674774
18 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.192_193delinsGGA (p.Ser64fs) Indel Pathogenic 4531 rs786205068 GRCh37: 11:62472792-62472793
GRCh38: 11:62705320-62705321
19 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.301_302insAA (p.Met101fs) Insertion Pathogenic 4532 rs786205069 GRCh37: 11:62462176-62462177
GRCh38: 11:62694704-62694705
20 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.315_316del (p.Tyr106fs) Deletion Pathogenic 4533 rs786205070 GRCh37: 11:62462162-62462163
GRCh38: 11:62694690-62694691
21 BSCL2 BSCL2, 258-BP DEL/12-BP INS Indel Pathogenic 4534 GRCh37:
GRCh38:
22 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.325dup (p.Thr109fs) Duplication Pathogenic 4536 rs786205071 GRCh37: 11:62462152-62462153
GRCh38: 11:62694680-62694681
23 BSCL2 , HNRNPUL2-BSCL2 NM_001122955.4(BSCL2):c.630+1G>A SNV Pathogenic 4538 GRCh37: 11:62462039-62462039
GRCh38: 11:62694567-62694567
24 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.636del (p.Tyr213fs) Deletion Pathogenic 4540 rs758843908 GRCh37: 11:62459883-62459883
GRCh38: 11:62692411-62692411
25 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.671+5G>A SNV Pathogenic 4541 rs786205072 GRCh37: 11:62459843-62459843
GRCh38: 11:62692371-62692371
26 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.672-3C>G SNV Pathogenic 4542 rs786205073 GRCh37: 11:62458896-62458896
GRCh38: 11:62691424-62691424
27 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.565G>T (p.Glu189Ter) SNV Pathogenic 4546 rs137852975 GRCh37: 11:62460143-62460143
GRCh38: 11:62692671-62692671
28 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.672-2A>C SNV Pathogenic 372118 rs766061024 GRCh37: 11:62458895-62458895
GRCh38: 11:62691423-62691423
29 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.193delinsGGA (p.Pro65fs) Indel Pathogenic 372116 rs1057517659 GRCh37: 11:62472792-62472792
GRCh38: 11:62705320-62705320
30 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.782dup (p.Ile262fs) Duplication Pathogenic 372120 rs749890533 GRCh37: 11:62458782-62458783
GRCh38: 11:62691310-62691311
31 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.574-2A>G SNV Pathogenic 372117 rs1013079991 GRCh37: 11:62459947-62459947
GRCh38: 11:62692475-62692475
32 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.672-2A>G SNV Pathogenic 372119 rs766061024 GRCh37: 11:62458895-62458895
GRCh38: 11:62691423-62691423
33 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.154_155dup (p.Tyr53fs) Duplication Pathogenic 372115 rs1057517658 GRCh37: 11:62472829-62472830
GRCh38: 11:62705357-62705358
34 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.652_662del (p.Ala218fs) Deletion Pathogenic 424623 rs1064797076 GRCh37: 11:62459857-62459867
GRCh38: 11:62692385-62692395
35 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.750dup (p.Leu251fs) Duplication Pathogenic 434545 rs1554983076 GRCh37: 11:62458814-62458815
GRCh38: 11:62691342-62691343
36 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.212+1G>T SNV Pathogenic 549713 rs1565152616 GRCh37: 11:62472772-62472772
GRCh38: 11:62705300-62705300
37 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.563_564GA[2] (p.Asn190fs) Microsatellite Pathogenic 549714 rs1565144681 GRCh37: 11:62460140-62460141
GRCh38: 11:62692668-62692669
38 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.210C>G (p.Tyr70Ter) SNV Pathogenic 549716 rs557044760 GRCh37: 11:62472775-62472775
GRCh38: 11:62705303-62705303
39 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.814-2A>G SNV Pathogenic 245977 rs879254029 GRCh37: 11:62458615-62458615
GRCh38: 11:62691143-62691143
40 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.317_321del (p.Tyr106fs) Deletion Pathogenic 4535 rs587777608 GRCh37: 11:62462157-62462161
GRCh38: 11:62694685-62694689
41 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.584C>T (p.Thr195Ile) SNV Pathogenic 623294 rs1565144468 GRCh37: 11:62459935-62459935
GRCh38: 11:62692463-62692463
42 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.412C>T (p.Arg138Ter) SNV Pathogenic 4537 rs137852970 GRCh37: 11:62462066-62462066
GRCh38: 11:62694594-62694594
43 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.634G>C (p.Ala212Pro) SNV Pathogenic 4539 rs137852971 GRCh37: 11:62459885-62459885
GRCh38: 11:62692413-62692413
44 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.823C>T (p.Arg275Ter) SNV Pathogenic 4545 rs137852974 GRCh37: 11:62458604-62458604
GRCh38: 11:62691132-62691132
45 AGPAT2 NM_006412.4(AGPAT2):c.202C>T (p.Arg68Ter) SNV Pathogenic 6624 rs104894093 GRCh37: 9:139571989-139571989
GRCh38: 9:136677537-136677537
46 AGPAT2 NM_006412.4(AGPAT2):c.589-2A>G SNV Pathogenic 6625 rs116807569 GRCh37: 9:139569261-139569261
GRCh38: 9:136674809-136674809
47 AGPAT2 NM_006412.4(AGPAT2):c.377dup (p.Pro128fs) Duplication Pathogenic 6626 rs387906355 GRCh37: 9:139571527-139571528
GRCh38: 9:136677075-136677076
48 AGPAT2 NM_006412.4(AGPAT2):c.415_417TTC[1] (p.Phe140del) Microsatellite Pathogenic 6628 rs387906356 GRCh37: 9:139571485-139571487
GRCh38: 9:136677033-136677035
49 AGPAT2 NM_006412.4(AGPAT2):c.493-1G>C SNV Pathogenic 6630 rs606231168 GRCh37: 9:139571133-139571133
GRCh38: 9:136676681-136676681
50 BSCL2 , HNRNPUL2-BSCL2 NM_032667.6(BSCL2):c.793C>T (p.Arg265Ter) SNV Pathogenic 143858 rs587777606 GRCh37: 11:62458772-62458772
GRCh38: 11:62691300-62691300

Expression for Congenital Generalized Lipodystrophy

Search GEO for disease gene expression data for Congenital Generalized Lipodystrophy.

Pathways for Congenital Generalized Lipodystrophy

Pathways related to Congenital Generalized Lipodystrophy according to GeneCards Suite gene sharing:

(show all 18)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.23 PPARG LEP INSR INS GZMB FOS
2
Show member pathways
12.68 PPARG LPIN1 LEP GPAT3 AGPAT2 AGPAT1
3
Show member pathways
12.61 LEP INSR INS FOS ADIPOQ
4
Show member pathways
12.33 LPIN1 GPAT3 AGPAT2 AGPAT1
5
Show member pathways
12.33 PPARG LEP INSR INS ADIPOQ
6
Show member pathways
12.25 INSR INS FOS AGPAT2 AGPAT1
7 12.19 PPARG LPIN1 INSR INS BSCL2 AGPAT2
8
Show member pathways
11.97 PPARG INSR INS ADIPOQ
9
Show member pathways
11.73 INSR INS ADIPOQ
10 11.68 PPARG LEP INS ADIPOQ
11 11.59 PPARG LPIN1 INS
12
Show member pathways
11.55 GPAT3 AGPAT2 AGPAT1
13 11.41 LPIN1 GPAT3 AGPAT2 AGPAT1
14 11.4 ZMPSTE24 PPARG LPIN1 LMNA LEP INS
15 11.32 INSR INS CAV1
16 11.26 LEP INSR INS CAV1
17 11.01 PPARG LEP ADIPOQ
18 10.7 PPARG LPIN1 LEP INSR ADIPOQ

GO Terms for Congenital Generalized Lipodystrophy

Cellular components related to Congenital Generalized Lipodystrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid droplet GO:0005811 9.5 CIDEC CAV1 BSCL2
2 endoplasmic reticulum membrane GO:0005789 9.5 ZMPSTE24 LPIN1 GPAT3 CAV1 BSCL2 AGPAT2
3 nuclear envelope GO:0005635 9.46 ZMPSTE24 LPIN1 LMNA INSR
4 caveola GO:0005901 9.43 INSR CAVIN1 CAV1
5 endoplasmic reticulum GO:0005783 9.4 ZMPSTE24 NHLRC1 LPIN1 GPAT3 FOS CIDEC

Biological processes related to Congenital Generalized Lipodystrophy according to GeneCards Suite gene sharing:

(show all 27)
# Name GO ID Score Top Affiliating Genes
1 response to drug GO:0042493 9.92 PPARG FOS AGPAT2 ADIPOQ
2 lipid metabolic process GO:0006629 9.91 PPARG LPIN1 LEP GPAT3 BSCL2 AGPAT2
3 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.77 LEP INSR INS
4 response to nutrient GO:0007584 9.76 PPARG LEP ADIPOQ
5 glucose metabolic process GO:0006006 9.71 LEP INS ADIPOQ
6 phospholipid biosynthetic process GO:0008654 9.67 GPAT3 AGPAT2 AGPAT1
7 phosphatidic acid biosynthetic process GO:0006654 9.65 GPAT3 AGPAT2 AGPAT1
8 negative regulation of lipid catabolic process GO:0050995 9.63 INS BSCL2
9 negative regulation of gluconeogenesis GO:0045721 9.63 INS ADIPOQ
10 fatty acid oxidation GO:0019395 9.62 PPARG ADIPOQ
11 positive regulation of glycogen biosynthetic process GO:0045725 9.61 INSR INS
12 fatty acid catabolic process GO:0009062 9.61 LPIN1 LEP
13 negative regulation of macrophage derived foam cell differentiation GO:0010745 9.59 PPARG ADIPOQ
14 neuron projection maintenance GO:1990535 9.58 INSR INS
15 positive regulation of glucose import GO:0046326 9.58 INSR INS ADIPOQ
16 positive regulation of cytokine-mediated signaling pathway GO:0001961 9.57 AGPAT2 AGPAT1
17 regulation of protein localization to nucleus GO:1900180 9.56 LMNA LEP
18 positive regulation of cytokine production GO:0001819 9.56 LEP INS AGPAT2 AGPAT1
19 negative regulation of acute inflammatory response GO:0002674 9.55 PPARG INS
20 glucose homeostasis GO:0042593 9.55 PPARG LEP INSR INS ADIPOQ
21 cellular response to hyperoxia GO:0071455 9.52 PPARG CAV1
22 positive regulation of respiratory burst GO:0060267 9.51 INSR INS
23 CDP-diacylglycerol biosynthetic process GO:0016024 9.5 GPAT3 AGPAT2 AGPAT1
24 positive regulation of developmental growth GO:0048639 9.46 LEP INSR
25 positive regulation of fatty acid metabolic process GO:0045923 9.43 PPARG ADIPOQ
26 cellular response to insulin stimulus GO:0032869 9.35 PPARG LPIN1 LEP INSR ADIPOQ
27 positive regulation of cold-induced thermogenesis GO:0120162 9.02 LPIN1 LEP CAV1 BSCL2 ADIPOQ

Molecular functions related to Congenital Generalized Lipodystrophy according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 insulin-like growth factor receptor binding GO:0005159 8.96 INSR INS
2 1-acylglycerol-3-phosphate O-acyltransferase activity GO:0003841 8.8 GPAT3 AGPAT2 AGPAT1

Sources for Congenital Generalized Lipodystrophy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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