Test Code 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.

Special Instructions

Method Name

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

Reporting Name

Cholestasis Gene Panel

Specimen Type

Varies

Specimen 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

Reject Due To

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

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.

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

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