Congenital Generalized Lipodystrophy (CGL) Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10157 AGPAT2 81479,81479 Order Options and Pricing
BSCL2 81406,81479
CAV1 81479,81479
CAVIN1 81479,81479
FBN1 81408,81479
KCNJ6 81479,81479
LMNA 81406,81479
PCYT1A 81479,81479
PPARG 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10157Genes x (9)81479 81406, 81408, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Congenital generalized lipodystrophies (CGL) are a group of heterogeneous disorders characterized by a near complete loss of adipose tissue at or soon-after birth (Patni and Garg. 2015. PubMed ID: 26239609; Akinci et al. 2018. PubMed ID: 30406415). These disorders are typically accompanied by severe metabolic dysregulation. The exact prevalence of CGL is unknown, but is estimated to be approximately 0.2 to 1 cases per million individuals (Chiquette et al. 2017. PubMed ID: 29066925).

CGL has four main subtypes, CGL1, CGL2, CGL3, and CGL4, which are associated with biallelic pathogenic variants in the AGPAT2, BSCL2, CAV1, and CAVIN1 (also known as PTRF) genes, respectively (Patni and Garg. 2015. PubMed ID: 26239609). CGL1 and CGL2 are also referred to as Berardinelli-Seip congenital lipodystrophy (BSCL; Van Maldergem. 2016. PubMed ID: 20301391). In addition to these four main subtypes, several genes are also known to present congenitally with generalized lipodystrophy as a primary clinical feature. These include the PPARG, PCYT1A, FBN1, LMNA, and KCNJ6 genes. Pathogenic variants in the PPARG and PCYT1A genes are associated with CGL-like presentations, pathogenic variants in the FBN1 and LMNA genes are associated with progeroid syndromes, and pathogenic variants in the KCNJ6 gene are associated with Keppen–Lubinsky syndrome (Akinci et al. 2018. PubMed ID: 30406415).

Clinical features associated with these disorders may include generalized lipodytrophy, a muscular appearance, prominent veins, accelerated growth, voracious appetite, umbilical hernias, hepatomegaly, splenomegaly, acanthosis nigricans, advanced bone age, and metabolic complications (insulin resistance, hypertriglyceridaemia, hepatic steatosis; Patni et al. 2015. PubMed ID: 26239609; Akinci et al. 2018. PubMed ID: 30406415). Female patients may also exhibit mild hirsutism, clitoromegaly, irregular menstrual periods, and polycystic ovaries. Clinical features associated with pathogenic variants in FBN1, KCNJ6, and LMNA may also include a marfanoid or progeroid appearance, as well as skeletal, cardiovascular and/or neurologic anomalies (Akinci et al. 2018. PubMed ID: 30406415). Medical management may include surveillance, psychological support, restriction of total fat intake, caloric restriction, increased physical activity, therapy for diabetes mellitus and hyperlipidemia, and possibly cosmetic surgery (Akinci et al. 2018. PubMed ID: 30370487). Genetic testing may aide in establishing a differential diagnosis and may assist reproductive planning.

Pathogenic variants in one or more of these genes included as part of this panel are reported to be associated with additional phenotypes including (but not limited to) familial partial lipodystrophy, encephalopathy, insulin resistance, severe obesity, skeletal dysplasia, neuropathy, muscular dystrophy, pulmonary hypertension, and Weill-Marchesani syndrome.

Genetics

CGL is primarily inherited in an autosomal recessive manner, however dominant inheritance is reported for the FBN1, KCNJ6, LMNA, and PPARG genes. Pathogenic variants may be inherited from a carrier parent, an affected parent, or arise de novo (Lightbourne and Brown. 2017. PubMed ID: 28476236). CGL is associated with small deletions, nonsense, splice site, frameshift, missense, and regulatory pathogenic variants. Structural variants, predominantly in the form of gross deletions, have been reported in isolated and familial cases of CGL (Agarwal et al. 2002. PubMed ID: 11967537; Purizaca-Rosillo et al. 2017. PubMed ID: 27868354).

The AGPAT2, BSCL2, CAV1 and CAVIN1 genes encode proteins that are involved in phospholipid and triglyceride synthesis, the fusion of lipid droplets, and the biogenesis of caveolae within adipocytes (Patni and Garg. 2015. PubMed ID: 26239609). The LMNA and PPARG genes encode proteins that are involved in adipocyte differentiation pathways (Evans et al. 2004. PubMed ID: 15057233; Capanni et al. 2005. PubMed ID: 15843404). The FBN1 gene encodes a glycoprotein that contributes to the strength and elasticity of tissues, regulates the bioavailability of transforming growth factor beta, and may be important in determining adipose tissue levels (Davis et al. 2016. PubMed ID: 27386756). The KCNJ6 gene encodes an inwardly rectifying potassium channel, which may be involved in the control of cellular processes such as adipogenic differentiation (Masotti et al. 2015. PubMed ID: 25620207; Van Maldergem. 2016. PubMed ID: 20301391).The PCYT1A gene encodes a rate-limiting enzyme in the in the CDP-choline or Kennedy pathway for de novo phosphatidylcholine biosynthesis (Wang et al. 2005. PubMed ID: 15798219).

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

Due to the genetic heterogeneity of the disorders tested in this panel, the clinical sensitivity of this specific grouping of genes is difficult to estimate. However, it is estimated that up to 80% of individuals with CGL have an identifiable genetic cause (Akinci et al. 2018. PubMed ID: 30406415).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with congenital generalized lipodystrophy.

Genes

Official Gene Symbol OMIM ID
AGPAT2 603100
BSCL2 606158
CAV1 601047
CAVIN1 603198
FBN1 134797
KCNJ6 600877
LMNA 150330
PCYT1A 123695
PPARG 601487
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Acromicric Dysplasia AD 102370
Benign Scapuloperoneal Muscular Dystrophy With Cardiomyopathy AD 181350
Charcot-Marie-Tooth Disease Type 2B1 AR 605588
Congenital Generalized Lipodystrophy Type 1 AR 608594
Congenital Generalized Lipodystrophy Type 2 AR 269700
Diabetes Mellitus, Noninsulin-Dependent AD 125853
Dilated Cardiomyopathy 1A AD 115200
Distal Hereditary Motor Neuronopathy Type 5 AD 600794
Ectopia Lentis, Isolated, Autosomal Dominant AD 129600
Emery-Dreifuss muscular dystrophy 3, AR AR 616516
Encephalopathy, progressive, with or without lipodystrophy AR 615924
Geleophysic Dysplasia 2 AD 614185
Heart-Hand Syndrome, Slovenian Type AD 610140
Hutchinson-Gilford Syndrome AR 176670
Keppen-Lubinsky syndrome AD 614098
Lipodystrophy, Congenital Generalized, Type 3 AR 612526
Lipodystrophy, Congenital Generalized, Type 4 AR 613327
Lipodystrophy, Familial Partial, Type 2 AD 151660
Lipodystrophy, Familial Partial, Type 3 AD 604367
Malouf Syndrome AD 212112
Mandibuloacral Dysplasia With Type A Lipodystrophy AR 248370
Marfan lipodystrophy syndrome AD 616914
Marfan Syndrome AD 154700
Mass Syndrome AD 604308
Muscular Dystrophy, Congenital, LMNA-Related AD 613205
Obesity AR 601665
Partial Lipodystrophy, Congenital Cataracts, and Neurodegeneration Syndrome AD 606721
Pulmonary hypertension, primary, 3 AD 615343
Restrictive Dermopathy, Lethal AR 275210
Spastic Paraplegia 17 AD 270685
Spondylometaphyseal Dysplasia with Cone-Rod Dystrophy AR 608940
Stiff Skin Syndrome AD 184900
Weill-Marchesani Syndrome 2 AD 608328

Related Tests

Name
PGxome®
Congenital Generalized Lipodystrophy (CGL) via the AGPAT2 Gene
Congenital Generalized Lipodystrophy (CGL) via the CAVIN1 (PTRF) Gene
Lipodystrophy and Heritable Pulmonary Arterial Hypertension via the CAV1 Gene
Seipin-Related Disorders via the BSCL2 Gene

Citations

  • Agarwal et al. 2002. PubMed ID: 11967537
  • Akinci et al. 2018. PubMed ID: 30370487
  • Akinci et al. 2018. PubMed ID: 30406415
  • Capanni et al. 2005. PubMed ID: 15843404
  • Chiquette et al. 2017. PubMed ID: 29066925
  • Davis et al. 2016. PubMed ID: 27386756
  • Evans et al. 2004. PubMed ID: 15057233
  • Lightbourne and Brown. 2017. PubMed ID: 28476236
  • Masotti et al. 2015. PubMed ID: 25620207
  • Patni and Garg. 2015. PubMed ID: 26239609
  • Purizaca-Rosillo et al. 2017. PubMed ID: 27868354
  • Van Maldergem. 2016. PubMed ID: 20301391
  • Wang et al. 2005. PubMed ID: 15798219

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Total Price: $
×
Copy Text to Clipboard
×