Cholestasis Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10319 ABCB11 81479,81479 Order Options and Pricing
ABCB4 81479,81479
ABCC2 81479,81479
ABCG5 81479,81479
ABCG8 81479,81479
ACOX2 81479,81479
AKR1D1 81479,81479
ALDOB 81479,81479
AMACR 81479,81479
ATP8B1 81479,81479
BAAT 81479,81479
CC2D2A 81479,81479
CFTR 81223,81222
CLDN1 81479,81479
CYP27A1 81479,81479
CYP7B1 81479,81479
DCDC2 81479,81479
DGUOK 81405,81479
DHCR7 81405,81479
FAH 81406,81479
GNAS 81479,81479
HNF1B 81405,81404
HSD17B4 81479,81479
HSD3B7 81479,81479
JAG1 81407,81406
KMT2D 81479,81479
LIPA 81479,81479
MKS1 81479,81479
MPV17 81405,81404
MYO5B 81479,81479
NOTCH2 81479,81479
NPC1 81406,81479
NPC2 81404,81479
NPHP1 81406,81405
NPHP3 81479,81479
NPHP4 81479,81479
NR1H4 81479,81479
PEX1 81479,81479
PEX10 81479,81479
PEX11B 81479,81479
PEX12 81479,81479
PEX13 81479,81479
PEX14 81479,81479
PEX16 81479,81479
PEX19 81479,81479
PEX2 81479,81479
PEX26 81479,81479
PEX3 81479,81479
PEX5 81479,81479
PEX6 81479,81479
PEX7 81479,81479
PKD1L1 81479,81479
PKHD1 81408,81479
POLG 81406,81479
SCYL1 81479,81479
SERPINA1 81479,81479
SLC10A1 81479,81479
SLC10A2 81479,81479
SLC25A13 81479,81479
SLC27A5 81479,81479
SLC51B 81479,81479
SLCO1B3 81479,81479
SMPD1 81479,81479
TALDO1 81479,81479
TJP2 81479,81479
TMEM216 81479,81479
TRMU 81479,81479
UGT1A1 81479,81479
VIPAS39 81479,81479
VPS33B 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10319Genes x (70)81479 81222, 81223, 81404, 81405, 81406, 81407, 81408, 81479 $990 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Hereditary cholestatic liver disease is a heterogenous group of disorders with complex pathophysiology, often presenting with overlapping symptoms such as jaundice, pruritus, failure to thrive, hepatomegaly, and other liver abnormalities (Santos et al. 2010. PubMed ID: 20425482; Karlsen et al. 2015. PubMed ID: 25920091; Sticova et al. 2018. PubMed ID: 30148122). At the molecular level, cholestasis is caused by a reduction of bile flow due to impaired hepatocyte secretion or obstruction of bile ducts as a result of defective hepatocyte transport, disorders of bile duct development, inborn errors of bile acid metabolism, and other metabolic disorders impacting the liver (Santos et al. 2010. PubMed ID: 20425482; Karlsen et al. 2015. PubMed ID: 25920091; Sticova et al. 2018. PubMed ID: 30148122; Sundaram et al. 2008. PubMed ID: 18577977; Grochowski et al. 2016. PubMed ID: 26548814; Fawaz et al. 2017. PubMed ID: 27429428). Hereditary cholestasis often, but not always, presents in the neonatal period, and may present with extrahepatic manifestations as well as systemic disease.

The estimated worldwide incidence of cholestasis ranges considerably depending on population. Pediatric cholestasis is estimated to affect about 1 in 2500 newborns (Karpen. 2020. PubMed ID: 32685137), while intrahepatic cholestasis of pregnancy is estimated to affect between ~0.1-5.2% of pregnancies worldwide, with up to ~9-25% of pregnancies affected in some South American populations (Lee et al. 2006. PubMed ID: 16761011; Floreani and Gervasi. 2016. PubMed ID: 26593298). The prevalence of cholestasis among patients with inflammatory bowel disease is as high as 7% (Girardin et al. 2018. PubMed ID: 29670889). Some hereditary forms of cholestatic liver disease are known to occur more frequently in ethnic groups where consanguineous marriage is prevalent or in some geographic regions due to founder effects (Gunaydin and Bozkurter Cil. 2018. PubMed ID: 30237746).

Advantages of genetic testing for cholestasis include confirmation of diagnosis, identification of other health risks associated with syndromic disease, allowing for targeted testing of other family members, and assistance with reproductive planning. This test especially aids in a differential diagnosis of similar phenotypes by simultaneously analyzing multiple genes that all include the clinical feature of cholestasis.

Genetics

Cholestatic liver disease is often multifactorial, resulting from a combination of metabolic, genetic, and environmental factors (Santos et al. 2010. PubMed ID: 20425482). Mendelian forms of cholestasis are most often inherited in an autosomal recessive manner, but may also be inherited in an autosomal dominant manner, or arise de novo. This test includes genes identified through literature, OMIM, and HGMD searches that have been reported to be associated with cholestasis.

An example of hereditary cholestatic liver disease due to defective hepatocyte transport includes progressive familial intrahepatic cholestasis (PFIC). Five types of PFIC have been classified in terms of causative genes involved in the hepatocellular transport system. Progressive familial intrahepatic cholestasis-1 (PFIC1) and progressive familial intrahepatic cholestasis-2 (PFIC2) are caused by hepatocyte membrane phospholipid asymmetry due to defects in ATP8B1 and ABCB11, respectively (Sticova et al. 2018. PubMed ID: 30148122). Progressive familial intrahepatic cholestasis-3 (PFIC3) is caused by reduced biliary phospholipid secretion due to pathogenic variants in ABCB4. Abnormal tight junctions between adjacent hepatocytes and biliary canaliculi in liver tissue due to TJP2 defects lead to progressive familial intrahepatic cholestasis-4 (PFIC4; Sambrotta et al. 2014. PubMed ID: 24614073). Defects in NR1H4, a key regulator of bile salt metabolism, cause familial intrahepatic cholestasis-5 (PFIC5; Sticova et al. 2018. PubMed ID: 30148122). PFIC is estimated to occur in 1 of 50,000-100,000 births (Davit-Spraul et al. 2009. PubMed ID: 19133130), and while de novo variants have been reported, the majority of causative variants are inherited (Francalanci et al. 2013. PubMed ID: 23437912). 

Alagille syndrome, an autosomal dominant disorder caused by defects in JAG1 and NOTCH2, is an example of hereditary cholestatic liver disease due to disordered bile duct development. JAG1 and NOTCH2 both encode components of the Notch signaling pathway, which is critical for proper development of the biliary tree (Adams and Jafar-Nejad. 2019. PubMed ID: 31615106). Alagille syndrome is estimated to occur in 1 of 70,000 births and 1 of 30,000 individuals overall (Turnpenny and Ellard. 2012. PubMed ID: 21934706; Hartley et al. 2013. PubMed ID: 23540503). Approximately 50-70% of cases have a de novo pathogenic variant (Spinner et al. 1993. PubMed ID: 20301450). 

A wide variety of causative variants in genes associated with cholestasis have been reported including missense, nonsense, splicing, small insertions and deletions, large deletions and duplications, and complex rearrangements (Human Gene Mutation Database). See individual gene summaries for information about the molecular biology of gene products and spectra of pathogenic variants.

Clinical Sensitivity - Sequencing with CNV PGxome

The detection rate of pathogenic variants in each gene of this panel in a large cohort of patients with cholestasis of undefined etiology is unknown. In a study of 51 subjects with cholestasis of undefined etiology, Matte et al. found causative variants in genes associated with PFIC in 14 patients (27%; Matte et al. 2010. PubMed ID: 20683201). In a study of 102 pediatric patients with various forms of cholestasis or idiopathic liver diseases, Chen et al. made a molecular diagnosis in 33 of 102 patients (32.4%) using a 44-gene panel (Chen et al. 2019. PubMed ID: 30366773). Those with progressive intrahepatic cholestasis or syndromic cholestasis in infancy had a diagnostic rate of 62.5% (Chen et al. 2019. PubMed ID: 30366773).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.5% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

This test does not currently include coverage for exons 1 to 4 of the NOTCH2 gene because of high sequence similarity to one or more additional chromosomal regions. So far, no pathogenic variants have been reported in these exons.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for this test are patients with cholestasis.

Diseases

Name Inheritance OMIM ID
ACTH-independent macronodular adrenal hyperplasia 219080
Adolescent Nephronophthisis AR 604387
Alagille Syndrome 1 AD 118450
Alagille Syndrome 2 AD 610205
Alpha-1-Antitrypsin Deficiency AR 613490
Alpha-Methylacyl-CoA Racemase Deficiency AR 614307
Arthrogryposis Renal Dysfunction Cholestasis Syndrome AR 208085
Arthrogryposis, Renal Dysfunction, And Cholestasis 2 AR 613404
Bardet-Biedl Syndrome 13 AR 615990
Benign Recurrent Intrahepatic Cholestasis 1 AR 243300
Benign Recurrent Intrahepatic Cholestasis 2 AR 605479
Bile Acid Malabsorption, Primary AR 613291
Bile Acid Synthesis Defect, Congenital, 1 AR 607765
Bile Acid Synthesis Defect, Congenital, 2 AR 235555
Bile Acid Synthesis Defect, Congenital, 3 AR 613812
Bile Acid Synthesis Defect, Congenital, 4 AR 214950
Bile acid synthesis defect, congenital, 6 AR 617308
Bilirubin, Serum Level Of, Quantitative Trait Locus 1 601816
Bronchiectasis AD 211400
Cerebrotendinous Xanthomatosis AR 213700
Charcot-Marie-Tooth disease, axonal, type 2EE AR 618400
Cholecystitis AD 600803
Cholestasis Of Pregnancy AD 147480
Cholestasis, intrahepatic, of pregnancy, 3 AD 614972
Cholestasis, Progressive Familial Intrahepatic 2 AR 601847
Cholestasis, Progressive Familial Intrahepatic 3 AR 602347
Cholestasis, Progressive Familial Intrahepatic 4 AR 615878
Cholestasis, progressive familial intrahepatic, 5 AR 617049
Chronic Obstructive Pulmonary Disease 606963
Citrin Deficiency AR 605814
Citrullinemia Type II AR 603471
COACH syndrome 2 619111
Congenital Bilateral Absence Of The Vas Deferens AR 277180
Congenital Microvillous Atrophy AR 251850
Crigler-Najjar Syndrome, Type I AR 218800
Crigler-Najjar Syndrome, Type II AR 606785
Cystic Fibrosis AR 219700
D-Bifunctional Protein Deficiency AR 261515
Deafness, Aminoglycoside-Induced MT 580000
Deafness, autosomal recessive 66 AR 610212
Deafness, congenital heart defects, and posterior embryotoxon 617992
Deficiency Of Transaldolase AR 606003
Diabetes Mellitus, Noninsulin-Dependent AD 125853
Dubin-Johnson Syndrome AR 237500
Fallot Tetralogy AD 187500
Gallbladder Disease 4 611465
Gilbert Syndrome AR 143500
Hajdu-Cheney Syndrome AD 102500
Heimler syndrome 1 AR 234580
Heimler syndrome 2 AR 616617
Hereditary Fructose Intolerance AR 229600
Heterotaxy, visceral, 8, autosomal AR 617205
Hypercholanemia, Familial AR 607748
Ichthyosis, Leukocyte Vacuoles, Alopecia, And Sclerosing Cholangitis AR 607626
Joubert Syndrome 2 AR 608091
Joubert Syndrome 28 AR 617121
Joubert Syndrome 4 AR 609583
Joubert Syndrome 9 AR 612285
Kabuki Syndrome 1 AD 147920
Liver Failure Acute Infantile AR 613070
Lucey-Driscoll Syndrome AR 237900
Lysosomal Acid Lipase Deficiency AR 278000
Maturity-Onset Diabetes Of The Young, Type 5 AD 137920
Meckel Syndrome 1 AR 249000
Meckel Syndrome 2 AR 603194
Meckel Syndrome 6 AR 612284
Meckel Syndrome 7 AR 267010
Mitochondrial DNA Depletion Syndrome 4B, Mngie Type AR 613662
Mitochondrial DNA-Depletion Syndrome 3, Hepatocerebral AR 251880
Navajo Neurohepatopathy AR 256810
Nephronophthisis AR 256100
Nephronophthisis 19 AR 616217
Nephronophthisis 4 AR 606966
Niemann-Pick Disease Type C1 AR 257220
Niemann-Pick Disease Type C2 AR 607625
Niemann-Pick Disease, Type A AR 257200
Niemann-Pick Disease, Type B AR 607616
Pancreatitis, Chronic AD 167800
Peroxisome biogenesis disorder 10A (Zellweger) AR 614882
Peroxisome biogenesis disorder 10B AR 617370
Peroxisome biogenesis disorder 11A (Zellweger) AR 614883
Peroxisome biogenesis disorder 11B AR 614885
Peroxisome biogenesis disorder 12A (Zellweger) AR 614886
Peroxisome biogenesis disorder 13A (Zellweger) AR 614887
Peroxisome Biogenesis Disorder 14B AR 614920
Peroxisome biogenesis disorder 1A (Zellweger) AR 214100
Peroxisome biogenesis disorder 1B (NALD/IRD) AR 601539
Peroxisome biogenesis disorder 2A (Zellweger) AR 214110
Peroxisome biogenesis disorder 2B AR 202370
Peroxisome biogenesis disorder 3A (Zellweger) AR 614859
Peroxisome biogenesis disorder 3B AR 266510
Peroxisome biogenesis disorder 4A (Zellweger) AR 614862
Peroxisome biogenesis disorder 4B AD 614863
Peroxisome biogenesis disorder 5A (Zellweger) AR 614866
Peroxisome biogenesis disorder 5B AR 614867
Peroxisome biogenesis disorder 6A (Zellweger) AR 614870
Peroxisome biogenesis disorder 6B AR 614871
Peroxisome biogenesis disorder 7A (Zellweger) AR 614872
Peroxisome biogenesis disorder 7B AR 614873
Peroxisome biogenesis disorder 8A, (Zellweger) AR 614876
Peroxisome biogenesis disorder 8B AR 614877
Peroxisome Biogenesis Disorder 9B AR 614879
Perrault Syndrome AR 233400
Pituitary adenoma 3, multiple types, somatic 617686
Polycystic Kidney Disease, Infantile Type AR 263200
Portal hypertension, noncirrhotic AR 617068
Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions 1 AD 157640
Progressive External Ophthalmoplegia With Mitochondrial DNA Deletions, Autosomal Recessive AR 258450
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 4 AR 617070
Progressive Intrahepatic Cholestasis AR 211600
Progressive Osseous Heteroplasia AD 166350
Progressive Sclerosing Poliodystrophy AR 203700
Pseudohypoparathyroidism Type 1A AD 103580
Pseudohypoparathyroidism Type 1B AD 603233
Pseudohypoparathyroidism Type 1C AD 612462
Pseudopseudohypoparathyroidism AD 612463
Renal Cell Carcinoma, Nonpapillary 144700
Renal Dysplasia And Retinal Aplasia AR 266900
Renal-Hepatic-Pancreatic Dysplasia AR 208540
Rhizomelic Chondrodysplasia Punctata Type 1 AR 215100
Rhizomelic chondrodysplasia punctata, type 5 AR 616716
Rotor syndrome 237450
Sclerosing cholangitis, neonatal AR 617394
Senior-Loken Syndrome 4 AR 606996
Sensory Ataxic Neuropathy, Dysarthria, And Ophthalmoparesis AR 607459
Sitosterolemia AR 210250
Sitosterolemia 2 AR 618666
Smith-Lemli-Opitz Syndrome AR 270400
Spastic Paraplegia 5A AR 270800
Spinocerebellar ataxia, autosomal recessive 21 AR 616719
Tyrosinemia Type I AR 276700

Related Test

Name
PGxome®
Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille syndrome Panel

Citations

  • Adams and Jafar-Nejad. 2019. PubMed ID: 31615106
  • Chen et al. 2019. PubMed ID: 30366773
  • Davit-Spraul et al. 2009. PubMed ID: 19133130
  • Fawaz et al. 2017. PubMed ID: 27429428
  • Floreani and Gervasi. 2016. PubMed ID: 26593298
  • Francalanci et al. 2013. PubMed ID: 23437912
  • Girardin et al. 2018. PubMed ID: 29670889
  • Grochowski et al. 2016. PubMed ID: 26548814
  • Gunaydin and Bozkurter Cil. 2018. PubMed ID: 30237746
  • Hartley et al. 2013. PubMed ID: 23540503
  • Human Gene Mutation Database (Biobase).
  • Karlsen et al. 2015. PubMed ID: 25920091
  • Karpen. 2020. PubMed ID: 32685137
  • Lee et al. 2006. PubMed ID: 16761011
  • Matte et al. 2010. PubMed ID: 20683201
  • Sambrotta et al. 2014. PubMed ID: 24614073
  • Santos et al. 2010. PubMed ID: 20425482
  • Spinner et al. 1993. PubMed ID: 20301450
  • Sticova et al. 2018. PubMed ID: 30148122
  • Sundaram et al. 2008. PubMed ID: 18577977
  • Turnpenny and Ellard. 2012. PubMed ID: 21934706

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

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