PMC Cholestasis Panel

Associated Conditions
- 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like (MEGDEL) syndrome
- ABCD3-related disorder of bile acid biosynthesis
- Acid sphingomyelinase (ASM) deficiency (Niemann-Pick disease type A and B)
- ACOX2-related disorder of bile acid biosynthesis
- Acyl-CoA oxidase deficiency
- Adenosine kinase deficiency
- Alagille syndrome (ALGS)
- Alagille syndrome 2 (ALGS2)
- ALG1-congenital disorder of glycosylation (ALG1-CDG, CDG-Ik)
- ALG8-congenital disorder of glycosylation (ALG8-CDG, CDG-Ih)
- Alpers-Huttenlocher (AHS)
- Alpha-1 antitrypsin deficiency (AATD)
- Alpha-methylacyl-CoA racemase deficiency (AMACR)
- Arginase deficiency
- Arthrogryposis, renal dysfunction, and cholestasis 1 (ARCS1)
- Arthrogryposis, renal dysfunction, and cholestasis 2 (ARCS2)
- Ataxia neuropathy spectrum (ANS)
- ATP6AP1 deficiency; ATP6AP1-congenital disorder of glycosylation (ATP6AP1-CDG)
- Autosomal recessive polycystic kidney disease (ARPKD)
- B4GALT1-congenital disorder of glycosylation (B4GALT1-CDG, CDG-IId)
- Benign recurrent intrahepatic cholestasis (BRIC)
- Bile acid amidation defect
- Bjornstad syndrome
- CALFAN syndrome
- Canty syndrome
- Carnitine-acylcarnitine translocase (CACT) deficiency
- CCDC115-congenital disorder of glycosylation (CCDC115-CDG, CDG2o)
- Cerebrotendinous xanthomatosis
- Charcot-Marie-Tooth disease type 2
- Childhood myocerebrohepatopathy spectrum (MCHS)
- Cholestasis with high gamma-glutamyltransferase
- Cholestatic liver disease
- Citrin deficiency
- Citrullinemia type I
- COG6-congenital disorder of glycosylation (COG6-CDG, CDG-IIL)
- COG7-congenital disorder of glycosylation (CDG-IIe)
- Combined oxidative phosphorylation deficiency 3 (COXPD3)
- Congenital bilateral absence of the vas deferens (CBAVD)
- Congenital bile acid synthesis
- Congenital bile acid synthesis defect type 1
- Congenital bile acid synthesis defect type 3 (CBAS3)
- Congenital dyserythropoietic anemia
- Crigler-Najjar syndrome types I and II
- Culler-Jones syndrome (CJS)
- Cystic fibrosis (CF)
- Cystinosis
- D-bifunctional protein deficiency (DBP),
- Dubin-Johnson syndrome
- Epilepsy
- Epimerase deficiency
- Erythropoietic protoporphyria
- Erythropoietic protoporphyria (EPP)
- Familial exudative vitreoretinopathy
- Familial hemophagocytic lymphohistiocytosis type 5 (FHL5)
- Familial hypercholanemia (FHCA)
- Familial transient neonatal hyperbilirubinemia
- Fumarate hydratase deficiency
- Galactosemia
- Gilbert syndrome
- Glucose-6-phosphate dehydrogenase deficiency (G6PD)
- GRACILE syndrome
- Growth restriction, impaired intellectual development, hypotonia, and hepatopathy (GRIDHH)
- Hajdu-Cheney syndrome
- Hearing loss
- Hemochromatosis type 3 (HFE3)
- Hereditary fructose intolerance
- Hereditary spastic paraplegia type 5A (SPG5A)
- Holoprosencephaly (HPE)
- Hyperbiliverdinemia
- Hypercholanemia with intractable itching, short stature, and intellectual disability
- Hypercholesterolemia
- Hypermanganesemia with dystonia
- Hyperornithinemia-hyperammonemia-homocystinuria (HHH) syndrome
- Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis syndrome
- Increased risk for chronic pancreatitis
- Intrahepatic cholestasis of pregnancy (IPC)
- Isolated adrenocorticotropic hormone (IAD)
- Isolated cholestasis
- ITCH deficiency
- Joubert syndrome and related disorders (JSRD)
- Kabuki syndrome
- Lathosterolosis
- Leigh syndrome
- Leukoencephalopathy with dystonia and motor neuropathy
- Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
- Low phospholipid associated cholelithiasis syndrome (LPAC)
- Low phospholipid associated cholelithiasis syndrome (LPAC)
- Lysosomal acid lipase (LAL) deficiency, Wolman disease
- McCune-Albright Syndrome
- MDR3 deficiency
- Meckel-Gruber syndrome
- MEDNIK syndrome
- Methylmalonic aciduria with homocystinuria due to cobalamin C (cblC) deficiency
- Mevalonate kinase deficiency
- Mevalonic aciduria
- Microvillus inclusion disease
- Mitchell-Riley syndrome
- Mitochondrial complex III deficiency
- Mitochondrial DNA depletion syndrome (MDS)
- Mitochondrial DNA depletion syndrome 7 (Infantile-onset spinocerebellar ataxia)
- Mitochondrial hepato-encephalopathy
- Mitochondrial trifunctional protein deficiency (MTP)
- Mitochondrial trifunctional protein deficiency (MTP)
- Myoclonic epilepsy myopathy sensory ataxia (MEMSA)
- Myopathy with excessive autophagy (MEAX)
- Neonatal cholestasis, intellectual disability and short stature
- Neonatal diabetes mellitus with congenital hypothyroidism (NDH)
- Neonatal sclerosing cholangitis (NSC)
- Nephronophthisis
- Niemann-Pick disease type C (NPC)
- North American Indian childhood cirrhosis (NAIC)
- Ornithine transcarbamylase (OTC) deficiency
- Perrault syndrome
- Perrault syndrome 5
- PKD1L1-related heterotaxy
- Porokeratosis
- Primary bile acid malabsorption
- Primary bile acid malabsorption-2 (PBAM2)
- Progressive external ophthalmoplegia
- Progressive familial intrahepatic cholestasis (PFIC)
- Progressive osseous heteroplasia (POH)
- Proopiomelanocortin deficiency (POMC)
- Pseudohypoparathyroidism (PHP)
- Pseudopseudohypoparathyroidism (PPHP) (Albright’s Hereditary Osteodystrophy)
- Renal cyst and diabetes syndrome
- Renal-hepatic-pancreatic dysplasia
- Rhizomelic chondrodysplasia punctata
- Sclerosing cholangitis, short stature, hypothyroidism and abnormal tongue pigmentation
- Sedoheptulokinase deficiency
- Senior-Loken syndrome, type 4
- Sitosterolemia
- Smith-Lemli-Opitz syndrome (SLOS)
- Snyder-Robinson syndrome
- Sterol carrier protein x deficiency,
- Tetralogy of Fallot
- TFAM-related mitochondrial DNA depletion syndrome
- Transaldolase deficiency (TALDO)
- TRAPC11-congenital disorder of glycosylation (TRAPC11-CDG); Limb-girdle muscular dystrophy type 2S
- TRMU-related transient infantile liver failure
- TTC26-related ciliopathy
- TWNK-related conditions:
- Tyrosinemia type 1
- VMA21-related congenital disorders of glycosylation (VMA21-CDG)
- Wilson disease
- X-linked sideroblastic anemia, X-linked erythropoietic protoporphyria
- Zellweger spectrum disorder (ZSD)

Methodology

Targeted Exome/ Slice Exome (Next Generation Sequencing including Copy Number Variation)

Coverage

120x

Ordering information

Turnaround Time: 10 business days

Preferred Speciment: Saliva Kits (available upon request)

Alternate Specimens: Nail clippings or 3-mL whole blood in purple top EDTA tube

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Limitations

All sequencing technologies have limitations. A negative result from this analysis does not rule out a possible genetic diagnosis as some variants may not be detected by this test. This test is not designed to detect low level mosaicism, structural rearrangements, indels >40bp, deep intronic variants of unknown clinical significance, or large cytogenetic CNVs. Certain inherent qualities of the human genome, for example repetitive regions/homopolymers, GC rich, pseudogenes, and rare polymorphisms, pose significant technical challenges such as sequence misalignment that may potentially impact the accuracy of the results. False negative results may also occur in the setting of allogeneic bone marrow, stem cell transplantation, active or chronic hematologic conditions, recent blood transfusions, suboptimal DNA quality or PCR trace contamination. Other potential sources of error include sample mix-ups and clerical issues.

References
- 1. Richards S et al. Genetics in medicine. 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. 2015 May;17(5):405-24 (PMID: 25741868)
- 2. GnomAD (gnomAD)
- 3. CSPEC (ClinGen variant classification rules registry) Criteria Specification Registry
- 4. Normal copy number variation in healthy individuals database of genomic variants: http://dgv.tcag.ca/dgv/app/home
- 5. Riggs, E.R., Andersen, E.F., Cherry, A.M. et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 22, 245–257 (2020). https://doi.org/10.1038/s41436-019-0686-8
- 6. Landrum MJ, Lee JM, Riley GR, Jang W, Rubinstein WS, Church DM, Maglott DR. ClinVar: public archive of relationships among sequence variation and human phenotype. Nucleic Acids Res. 2014 Jan 1;42(1):D980-5. doi: 10.1093/nar/gkt1113. PubMed PMID: 24234437.
- 7. Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), Copyright® 1966-2012. World Wide Web URL: http://omim.org.
- 8. http://tinyurl.com/ACMGv4 (ACMG/ Clingen draft Interpretation SOP); clingen_variant-curation_sopv1.pdf

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Test Description

Associated Conditions

Methodology

Coverage

Ordering information

Limitations

References

Tagged Genes