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Test Code HYPBG Hypobetalipoproteinemia Gene Panel, Varies


Ordering Guidance


This gene panel contains genes in common with HCHLG / Hypercholesterolemia Gene Panel, Varies. These tests should not be ordered concurrently as they assist in diagnosing conflicting disorders. For low levels of cholesterol (hypocholesterolemia), order this test. For high levels of cholesterol (hypercholesterolemia), order HCHLG.

 

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. To modify this panel via CGPH, use the Cardiovascular/Connective Tissue/Dyslipidemia/Cerebrovascular/Primary Ciliary Dyskinesia disease state for step 1 on the Custom Gene Ordering Tool.

 

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.



Shipping Instructions


 



Necessary Information


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



Specimen Required


Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a hematopoietic stem cell transplant, call 800-533-1710.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

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

Acceptable: Green top (Sodium heparin)

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) 4 days/Refrigerated 4 days/Frozen 4 days

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.

2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.

 

Specimen Type: Cord blood

Container/Tube:

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

Acceptable: Green top (Sodium heparin)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

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

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.

2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.

3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

 

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Collection Kit (T786)

Specimen Volume: 2 Swabs

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days

Additional information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.

 

Specimen Type: Cultured fibroblasts

Source: Skin

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy. Cultured cells from a prenatal specimen will not be accepted.

Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours

Additional Information:

1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.

2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Tissue biopsy

Supplies: Hank's Solution (T132)

Container/Tube: Sterile container with sterile Hank's balanced salt solution, Ringer's solution, or normal saline.

Specimen Volume: 0.5 to 3 cm(3) or larger

Specimen Stability Information: Ambient (preferred) <24 hours/Refrigerated <24 hours

Additional Information:

1. Specimens are preferred to be received within 24 hours of collection. Culture and extraction will be attempted for specimens received after 24 hours and will be evaluated to determine if testing may proceed.

2. A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks are required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Blood spot

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Container/Tube:

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: PerkinElmer 226 filter paper or blood spot collection card

Specimen Volume: 2 to 5 Blood spots

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year is a fingerstick. For detailed instructions, see How to Collect a Dried Blood Spot Sample.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for a minimum of 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry.

Specimen Stability Information:: Ambient (preferred)/Refrigerated

Additional Information:

1. Blood spot specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from blood spots, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.

2. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.

3. For collection instructions, see Blood Spot Collection Instructions

4. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)

5. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)

 

Specimen Type: Extracted DNA

Container/Tube:

Preferred: Screw Cap Micro Tube, 2 mL with skirted conical base

Acceptable: Matrix tube, 1 mL

Collection Instructions:

1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated

Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.


Forms

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. Hypobetalipoproteinemia Gene Panel (HYPBG) Prior Authorization Ordering Instructions

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

Secondary ID

617309

Useful For

Providing a genetic evaluation for patients with a personal or family history suggestive of familial hypobetalipoproteinemia

Method Name

Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

Reporting Name

Hypobetalipoproteinemia Gene Panel

Specimen Type

Varies

Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Reject Due To

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Clinical Information

Monogenic causes of hypobetalipoproteinemia include familial hypobetalipoproteinemia (FHBL), abetalipoproteinemia (ABL), chylomicron retention disease (CMRD), loss-of-function variants in PCSK9, and familial combined hypolipidemia (FCH).

Familial hypobetalipoproteinemia is the most common form of hypobetalipoproteinemia and is characterized by apolipoprotein B (ApoB) levels below the 5th percentile and low-density lipoprotein cholesterol (LDL-C) concentrations in the range of 20 mg/dL to 50 mg/dL. FHBL displays codominant inheritance, whereby heterozygous individuals may be asymptomatic or have mild disease, and (rare) compound heterozygous and homozygous individuals develop more severe, early-onset disease. In cases of mild to moderate FHBL with little or no liver involvement, prognosis is good and, in fact, may be associated with increased longevity. In severe disease, symptoms include fatty liver, which may progress to cirrhosis over time, symptoms of fat malabsorption, failure to thrive, and neurological and ocular dysfunction. FHBL is most commonly due to disease-causing truncating variants in the APOB gene resulting in reduced or nonfunctional protein.

 

Abetalipoproteinemia is a rare (<1:1,000,000) condition characterized by triglyceride concentrations of less than 30 mg/dL, cholesterol concentrations of less than 30 mg/dL, and undetectable LDL and ApoB levels. Clinical presentation is similar to that described above for compound heterozygous and homozygous FHBL. ABL displays autosomal recessive inheritance and is caused by compound heterozygous or homozygous disease-causing variants in the MTTP gene.

 

Chylomicron retention disease is a rare lipid malabsorption syndrome that typically presents in young infants with diarrhea, steatorrhea, abdominal distention, and failure to thrive. Laboratory findings include LDL-C and high-density lipoprotein cholesterol-C reduction of approximately 50% with normal triglyceride concentrations. CMRD displays autosomal recessive inheritance and is caused by compound heterozygous or homozygous disease-causing variants in the SAR1B gene.

 

Heterozygous loss-of-function variants in the PCSK9 gene are associated with mild to moderate reduction in LDL-C and normal health with significantly lower prevalence of atherosclerotic heart disease. Rare individuals with biallelic loss-of-function variants in PCSK9 have been reported with extremely low levels of LDL-C (approximately 15 mg/dL), normal health and reproductive capacity, and no evidence of neurologic or cognitive dysfunction. Notably, heterozygous gain-of-function variants in PCSK9 are associated with familial hypercholesterolemia.

 

Finally, FCH is a very rare condition of panhypolipidemia associated with normal health and significantly lower prevalence of atherosclerotic heart disease. This condition is caused by loss-of-function variants in the ANGPTL3 gene. Similar to FHBL and PCSK9, FCH displays codominant inheritance, with heterozygotes having normal HDL-C and LDL-C concentrations that are below the 25th percentile, while compound heterozygous and homozygous individuals display significant reductions in HDL-C levels as well.

Reference Values

An interpretive report will be provided.

Interpretation

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions

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 mutations 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. For the most up to date list of genes included in this test and 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:

Currently, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages healthcare professionals 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.(1) 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.

Clinical Reference

1. 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;17(5):405-424

2. Shapiro MD and Feingold KR. Monogenic disorders causing hypobetalipoproteinemia. In: Feingold KR, Anawalt B, Boyce A, et al, eds. Endotext [Internet]. MDTest.com, Inc; 2000. Updated January 22, 2024. Accessed March 31, 2025. Available at www.ncbi.nlm.nih.gov/books/NBK326744/

Method Description

Next-generation sequencing (NGS) and/or Sanger sequencing is 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 deletions-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. Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

 

 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 Hypobetalipoproteinemia Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)

 

Genes analyzed: ANGPTL3, APOB, MTTP, PCSK9, and SAR1B

Day(s) Performed

Varies

Report Available

21 to 28 days

Specimen Retention Time

Whole blood: 28 days (if available); Salvia: 30 days (if available); Extracted DNA: 3 months; Blood spots: 1 year Whole

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

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.

CPT Code Information

81406

81407

81479

81479 (if appropriate for government payers)

88233-Tissue culture, skin, solid tissue biopsy (if appropriate)

88240-Cryopreservation (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HYPBG Hypobetalipoproteinemia Gene Panel 51966-0

 

Result ID Test Result Name Result LOINC Value
617310 Test Description 62364-5
617311 Specimen 31208-2
617312 Source 31208-2
617313 Result Summary 50397-9
617314 Result 82939-0
617315 Interpretation 69047-9
617316 Additional Results 82939-0
617317 Resources 99622-3
617318 Additional Information 48767-8
617319 Method 85069-3
617320 Genes Analyzed 48018-6
617321 Disclaimer 62364-5
617322 Released By 18771-6

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

Skin biopsy: For skin biopsy or cultured fibroblast specimens, a fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.