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HelpTest ID: CHLGP Cholestasis Gene Panel, Varies
Ordering Guidance
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.
Shipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA) or yellow top (ACD)
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 14 days
Specimen Type: Skin biopsy
Supplies: Fibroblast Biopsy Transport Media (T115)
Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin (Eagle's minimum essential medium with 1% penicillin and streptomycin).
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.
Specimen Type: Cultured fibroblast
Container/Tube: T-25 flask
Specimen Volume: 2 Flasks
Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.
Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)
Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is 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 (formerly Ahlstrom 226) filter paper or blood spot collection card
Specimen Volume: 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 Dried Blood Spot Samples.
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. Due to lower concentration of DNA yielded from blood spot, it is possible that additional specimen may be required to complete testing.
2. For collection instructions, see Blood Spot Collection Instructions
3. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777)
4. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800)
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 1 Swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient 30 days
Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.
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. Molecular Genetics: Biochemical Disorders Patient Information (T527)
3. If not ordering electronically, complete, print, and send a Biochemical Genetics Test Request (T798) with the specimen.
Useful For
Establishing a molecular diagnosis for patients with monogenic cholestasis
Identifying variants within genes known to be associated with primary, monogenic cholestasis, allowing for predictive testing of at-risk family members
This panel is not intended to diagnose multifactorial cholestasis.
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 112 genes associated with cholestasis: ABCB11, ABCB4, ABCC2, ABCG5, ABCG8, ABHD5, ACOX1, AGL, AGPAT2, AKR1D1, ALDOA ,ALDOB, AMACR, ARSB, ASAH1, ATP8B1, BAAT, BSCL2, CAVIN1, CC2D2A, CIDEC, CLDN1, CFTR, CYP27A1, CYP7A1, CYP7B1, DCDC2, DGUOK, DHCR7, EHHADH, FAH, FBP1, FUCA1, G6PC, GAA, GALNS, GBA, GBE1, GLB1, GNE, GNPTAB, GNS, GUSB, HADHA, HGSNAT, HNF1B, HSD17B4, HSD3B7, IDS, IDUA, INVS, JAG1, KCNH1, LIPA, MAN2B1, MKS1, MPV17, MVK, NAGLU, NEU1, NOTCH2, NPC1, NPC2, NPHP1, NPHP3, NPHP4, NR1H4, PEPD, PEX1, PEX10, PEX11B, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6, PEX7, PHKA2, PHKB, PHKG2, PKHD1, PNPLA2, POLG, PRKAG2, PSAP, PYGL, SCP2, SERPINA1, SGSH, SLC10A1, SLC10A2, SLC17A5, SLC25A13, SLC27A5, SLC37A4, SLC7A7, SMPD1, SUMF1, TALDO1, TJP2, TMEM216, TRIM37, TRMU, UGT1A1, VIPAS39, VPS33A, and VPS33B.See Targeted Genes and Methodology Details for Cholestasis 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 disorders causing primary, monogenic cholestasis. Risk alleles for multifactorial cholestasis will not be reported unless otherwise requested.
Method Name
Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing.
Reporting Name
Cholestasis Gene PanelSpecimen Type
VariesSpecimen Minimum Volume
Blood: 1 mL; Blood spots: 2 spots; Skin biopsy, cultured fibroblasts, or saliva: See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Clinical Information
Cholestasis is a decrease in or obstruction of bile flow that results in jaundice, pruritus, hepatomegaly, and splenomegaly. Cholestasis can be the primary clinical symptom due to progressive familial intrahepatic cholestasis (PFIC) or one of a number of symptoms due to a variety of genetic disorders that cause multisystem disease. Many forms of cholestasis are multifactorial in origin occurring due to the presence of both risk-associated alleles and environmental circumstances. This panel is not intended to diagnose multifactorial cholestasis and risk-associated alleles will not be reported unless requested.
PFIC is a group of disorders caused by bile secretion or transport defects that result in intrahepatic cholestasis in infancy or childhood. There are 5 types of PFIC that are molecularly defined: FIC1 (ATP8B1 gene), PFIC2 (ABCB11 gene), PFIC3 (ABCB4 gene), PFIC4 (TJP2 gene), and PFIC5 (NR1H4 gene). PFICs 1, 2, and 4 have normal to mild elevations of gamma-glutamyltransferase (GGT). PFIC 3 results in significantly elevated serum GGT, whereas PFIC5 causes low to normal GGT levels.
PFIC can present with cholestasis in neonates, but most commonly manifests around 3 months of age for those with PFIC2, the most common type. Studies of infants and children with cholestasis have shown that 12% to 13% have molecularly confirmed PFIC. Disease progression results in liver failure and hepatocellular carcinoma. Liver transplantation is an effective treatment, though less effective for multisystemic PFIC1 than for other types. However, there is significant mortality, as 87% of patients with untreated PFIC will not survive.
A variety of other genetic disorders can also result in cholestasis, such as Alagille syndrome (JAG1 and NOTCH2 genes), alpha-1-antitrypsin deficiency (SERPINA1 gene), arthrogryposis, kidney dysfunction, and cholestasis syndrome (VPS33B and VIPAS39 genes), citrullinemia (SLC25A13 gene), congenital defects of bile acid synthesis (HSD3B7 and AKR1D1 genes), familial hypercholanemia (BAAT gene), neonatal ichthyosis-sclerosing cholangitis syndrome (CLDN1 gene), and Crigler-Najjar syndrome types I or II or Gilbert syndrome (UGT1A1). In addition, peroxisomal disorders (PEX genes) and mitochondrial disorders can include cholestatic liver disease among other features.
This comprehensive gene panel is a rapid and reliable first-tier test to establish a diagnosis for patients with monogenic cholestasis.
Reference Values
An interpretive report will be provided.
Interpretation
All detected alterations 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.
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. Baker A, Kerkar N, Todorova L, et al: Systematic review of progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol. 2019;43(1):20-36
3. Chowdhury J, Wolkoff AW, Chowdhury N, Arias IM: Hereditary jaundice and disorders of bilirubin metabolism. In: Valle D, Antonarakis S, Ballabio A, Beaudet A, Mitchell GA, eds. The Online Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill; 2019. Accessed September 08, 2022. Available at http://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225541453
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
81443
88233-Tissue culture, skin, solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| CHLGP | Cholestasis Gene Panel | 105345-3 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 608620 | Test Description | 62364-5 |
| 608621 | Specimen | 31208-2 |
| 608622 | Source | 31208-2 |
| 608623 | Result Summary | 50397-9 |
| 608624 | Result | 82939-0 |
| 608625 | Interpretation | 69047-9 |
| 608626 | Resources | 99622-3 |
| 608627 | Additional Information | 48767-8 |
| 608628 | Method | 85069-3 |
| 608629 | Genes Analyzed | 48018-6 |
| 608630 | Disclaimer | 62364-5 |
| 608631 | Released By | 18771-6 |
Day(s) Performed
Varies
Report Available
21 to 28 daysReflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CULFB | Fibroblast Culture for Genetic Test | Yes | No |
Testing Algorithm
For skin biopsy and cultured fibroblast specimens, fibroblast culture will be added at an additional charge. If viable cells are not obtained, the client will be notified.
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