Test Id : LIPOG

Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.

Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.

Specimen preferred to arrive within 96 hours of collection.

Prior Authorization is available, but not required, for this test. If proceeding with the prior authorization process, submit the required form with the specimen.

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred)/Refrigerated

• Informed Consent for Genetic Testing
• Informed Consent for Genetic Testing (Spanish)
• Hereditary Dyslipidemia Patient Information
• Targeted Genes and Methodology Details for Lipodystrophy Gene Panel
• Lipodystrophy Gene Panel (LIPOG) Prior Authorization Ordering Instructions

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file.

The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing (Spanish) (T826)

2. Hereditary Dyslipidemia Patient Information

3. Lipodystrophy Gene Panel (LIPOG) Prior Authorization Ordering Instructions

4. If not ordering electronically, complete, print, and send a Cardiovascular Test Request (T724) with the specimen.

1 mL

Providing a genetic evaluation for patients with a personal or family history suggestive of a hereditary lipodystrophy

Establishing a diagnosis of a hereditary lipodystrophy

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 12 genes associated with hereditary lipodystrophy: AGPAT2, BSCL2, CAV1, CAVIN1, FBN1, KCNJ6, LIPE, LMNA, PIK3R1, PLIN1, PPARG, and ZMPSTE24. See Targeted Genes and Methodology Details for Lipodystrophy Gene Panel and Method Description for additional details.

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for hereditary lipodystrophy.

Prior Authorization is available for this assay.

Lipodystrophies are rare conditions characterized primarily by the inability to properly store adipose tissue in the absence of nutritional deficit or catabolic state.(1) Lipodystrophies can be genetic (hereditary) or acquired (caused by environmental factors such as illness). The two most common forms of hereditary lipodystrophies are congenital generalized lipodystrophy (CGL) and familial partial lipodystrophy (FPLD), which are named according to the regions of the body they affect.(1)

CGL (also known as Berardinelli-Seip congenital lipodystrophy) is an autosomal recessive condition characterized by generalized absence fat throughout the entire body, generalized muscular appearance, and metabolic complications such as diabetes mellitus and dyslipidemia.(1,2) The prevalence of autosomal recessive CGL is not well-established, with estimates ranging from 1:10,000,000 to 1:25,000 depending on the population being considered.(2) Severe CGL is also a feature of Keppen-Lubinsky syndrome (KPLBS), an extremely rare autosomal dominant condition caused by biallelic, disease-causing variants in the KCNJ6 gene. KPLBS is a syndromic condition characterized by severe generalized lipodystrophy, microcephaly, progeroid appearance, and intellectual disability.(3)

FPLD can be inherited in an autosomal dominant or autosomal recessive manner and is characterized by localized absence of fat in the limbs with possible metabolic complications.(1,4) FPLD can be isolated or can be a feature of a syndromic condition such as autosomal dominant SHORT syndrome (short stature, hyperextensibility of joints, ocular depression, Rieger anomaly, and teething delay) and autosomal recessive Mandibuloacral dysplasia with type B lipodystrophy.(4) The prevalence of FPLD is not known but thought to be rare.(4)

Disease-causing variants in the LMNA gene can lead to autosomal recessive and autosomal dominant forms of lipodystrophies, but variants in this gene are also associated with several autosomal dominant cardiac, connective tissue, and muscular dystrophy phenotypes.(4) Often, lipodystrophy is a single feature of a more syndromic condition when caused by disease-causing LMNA variants.(4)

The FBN1 gene is primarily associated with autosomal dominant Marfan syndrome without features of lipodystrophy. However, literature suggests that specific disease-causing variants in the FBN1 gene may lead to an overlapping phenotype characterized by partial features of Marfan syndrome, progeroid appearance, and clinical features of lipodystrophy.(5)

An interpretive report will be provided.

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(6) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Clinical Correlations:
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact the Mayo Clinic Laboratories genetic counselors at 800-533-1710.

Technical Limitations:
Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

Deletion/Duplication Analysis:

This analysis targets single and multi-exon deletions/duplications; however, in some instances single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

Genes may be added or removed based on updated clinical relevance. Refer to the Targeted Genes and Methodology Details for Lipodystrophy Gene Panel for the most up to date list of genes included in this test. For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

Reclassification of Variants:
At this time, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time.

Variant Evaluation:
Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(6) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.  

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools should be interpreted with caution and professional clinical judgment.

Rarely, incidental or secondary findings may implicate another predisposition or presence of active disease. Incidental findings may include, but are not limited to, results related to the sex chromosomes. These findings will be carefully reviewed to determine whether they will be reported.

1. Brown RJ, Araujo-Vilar D, Cheung PT, et al: The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline. J Clin Endocrinol Metab. 2016 Dec;101(12):4500-4511. doi: 10.1210/jc.2016-2466

2. Van Maldergem L: Berardinelli-Seip congenital lipodystrophy. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2003. Updated December 8, 2016. Accessed July 26, 2022. Available at www.ncbi.nlm.nih.gov/books/NBK1212/

3. Masotti A, Uva P, Davis-Keppen L, et al: Keppen-Lubinsky syndrome is caused by mutations in the inwardly rectifying K+ channel encoded by KCNJ6. Am J Hum Genet. 2015 Feb;96(2):295-300. doi: 10.1016/j.ajhg.2014.12.011

4. Bagias C, Xiarchou A, Bargiota A, Tigas S: Familial partial lipodystrophy (FPLD): recent insights. Diabetes Metab Syndr Obes. 2020 May;13:1531-1544. doi: 10.2147/DMSO.S206053

5. Passarge E, Robinson PN, Graul-Neumann LM: Marfanoid-progeroid-lipodystrophy syndrome: a newly recognized fibrillinopathy. Eur J Hum Genet. 2016 Aug;24(9):1244-1247. doi: 10.1038/ejhg.2016.6

6. Richards S, Aziz N, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424. doi: 10.1038/gim.2015.30

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletion/insertions (delins)less than 40 base pairs (bp), above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Lipodystrophy Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

Genes analyzed: AGPAT2, BSCL2, CAV1, CAVIN1, FBN1, KCNJ6, LIPE, LMNA, PIK3R1, PLIN1, PPARG, and ZMPSTE24

Varies

• Authorized users can sign in to Test Prices for detailed fee information.
• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their account representative. For assistance, contact Customer Service.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

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Insurance preauthorization is available for this testing; forms are available.

Patient financial assistance may be available to those who qualify. Patients who receive a bill from Mayo Clinic Laboratories will receive information on eligibility and how to apply.