Cholestasis NGS Panel

Test Information

This panel of 73 genes is intended for patients with cholestasis, and it is performed by Next Generation Sequencing (NGS).

Turnaround Time

5 weeks

CPT Code(s)





  • ABCB11
  • ABCB4
  • ABCC2
  • ABCG5
  • ABCG8
  • AKR1D1
  • ATP8B1
  • BAAT
  • CC2D2A
  • CFTR
  • CLDN1
  • CYP27A1
  • CYP7A1
  • CYP7B1
  • DCDC2
  • DHCR7
  • FAH
  • GPBAR1
  • HNF1B
  • HSD17B4
  • HSD3B7
  • INVS
  • JAG1
  • LCT
  • LIPA
  • MKS1
  • MPV17
  • MYO5B
  • NOTCH2
  • NPC1
  • NPC2
  • NPHP1
  • NPHP3
  • NPHP4
  • NR1H4
  • PEX1
  • PEX10
  • PEX11B
  • PEX12
  • PEX13
  • PEX14
  • PEX16
  • PEX19
  • PEX2
  • PEX26
  • PEX3
  • PEX5
  • PEX6
  • PEX7
  • PKHD1
  • POLG
  • SCP2
  • SCYL1
  • SLC10A1
  • SLC10A2
  • SLC25A13
  • SLC27A5
  • SLC26A3
  • SMPD1
  • SPINT2
  • TJP2
  • TMEM216
  • TRMU
  • SKIC3
  • UGT1A1
  • VPS33B

Clinical Information

Cholestasis results from restricted flow of bile due to obstruction or reduced secretion. Neonatal cholestasis is characterized by elevated direct (conjugated) bilirubin (>1-2 mg/dL), and it is present in approximately 1 in 2500 full-term infants. While jaundice due to elevated indirect, or unconjugated, bilirubin is common, jaundice that occurs within the first 24 hours of life or persists past two weeks of age, occurs in formula-fed infants, or results from increased direct/conjugated bilirubin warrants further evaluation and treatment. The most common cause of neonatal cholestasis is biliary atresia, but genetic and/or metabolic disorders are frequent reasons as well. In addition to jaundice, clinical findings may include dark-colored urine, acholic stools, and hepatomegaly. The most common genetic cause of neonatal cholestasis is Alagille syndrome which is characterized by dysmorphic features, cardiac defects, kidney abnormalities, pancreatic insufficiency, and skeletal changes. Other genetic conditions include peroxisome biogenesis disorders (Zellweger syndrome), cystic fibrosis, Smith-Lemli-Opitz syndrome, and a variety of inborn errors of metabolism. In addition to the neonatal period, cholestasis can present at any age from infancy to childhood or adolescence to adulthood. Women with genetic predispositions may present with intrahepatic cholestasis of pregnancy (ICP) as well as with use of oral contraceptives, and these situations may resolve after delivery or discontinuation of oral contraceptives. Symptoms can occur in an episodic manner and include pruritus, jaundice, gallstones, hepatic fibrosis, cirrhosis, and abnormal liver function studies. Conditions including alpha-1-antitrypsin deficiency may increase the risk for adult-onset cholestasis. Severity ranges significantly from a relatively benign but recurrent course to death from end-stage liver disease. Treatments vary depending on the underlying condition and may include laboratory monitoring, medication, cholecystectomy, or liver transplant. The majority of cholestatic conditions are inherited in an autosomal recessive pattern, but a few conditions demonstrate autosomal dominant inheritance.


For patients with a specific suspected disorder, individual gene sequencing should be considered first. Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.


Next Generation Sequencing


The current design of this panel covers all genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel may be confirmed with Sanger sequencing. Novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations, and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution microarray to complement the sequencing. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.

Specimen Requirements

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

Transport Instructions

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

Prenatal Testing Information

If pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.

Have Questions? Need Support?

Call our laboratory at 1-800-473-9411 or contact one of our Laboratory Genetic Counselors for assistance.
Robin Fletcher, MS, CGC
Falecia Thomas, MS, CGC
Alex Finley, MS, CGC

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