ABCB11, ABCB4, ABCC2, ABCG5, ABCG8, AKR1D1, ALDOB, AMACR, ATP8B1, BAAT, CC2D2A, CFTR, CLDN1, CYP27A1, CYP7A1, CYP7B1, DCDC2, DGUOK, DHCR7, EHHADH, EPCAM, FAH, GPBAR1, HNF1B, HSD17B4, HSD3B7, INVS, JAG1, LCT, LIPA, MKS1, MPV17, MYO5B, NEUROG3, 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, SERPINA1, SLC10A1, SLC10A2, SLC25A13, SLC27A5, SLC26A3, SMPD1, SPINT2, TJP2, TMEM216, TRMU, SKIC3, UGT1A1, VPS33B, VIPA39
Cholestasis NGS Panel
Cholestasis NGS Panel
The Cholestasis NGS Panel is a 74-gene panel intended for patients with a diagnosis or clinical suspicion of cholestasis.
Alagille syndrome, Alpha-methylacyl-coa racemase deficiency, Arthrogryposis\, renal dysfunction\, and cholestasis 2, Benign recurrent intrahepatic cholestasis, Bile acid synthesis defect, Cerebrotendinous xanthomatosis, Cholestasis, Cholesteryl ester storage disease, Citrullinemia type II, Congenital bilateral aplasia of the vas deferens, Congenital lactase deficiency, Congenital malabsorptive diarrhea, Congenital secretory chloride diarrhea, Congenital tufting enteropathy, Crigler najjar syndrome, Cystic fibrosis, D-bifunctional protein deficiency, Dubin-Johnson syndrome, Emphysema due to AAT deficiency, Familial hypercholanemia, Gallbladder disease, Hajdu-Cheney syndrome, Heimler syndrome, Hereditary fructose intolerance, Ichthyosis\, leukocyte vacuoles\, alopecia\, and sclerosing cholangitis, Intrahepatic cholestasis of pregnancy, Leukoencephalopathy with dystonia and motor neuropathy, Meckel syndrome, Microvillus inclusion disease, Neonatal sclerosing cholangitis, Nephronophthisis, Niemann-Pick disease, Noncirrhotic portal hypertension, Peroxisome biogenesis disorder (Zellweger syndrome), Perrault syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, Progressive familial intrahepatic cholestasis, Renal cysts and diabetes syndrome, Renal-hepatic-pancreatic dysplasia, Rhizomelic chondrodysplasia punctata, Senior-Loken syndrome, Sitosterolemia, Smith-Lemli-Opitz syndrome, Transient familial neonatal hyperbilirubinemia, Transient infantile liver failure, Tyrosinemia, Wolman disease
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.
Technical Information
This panel is performed by Next Generation Sequencing and covers the coding regions of the listed genes and the flanking intronic sequences. Promoter, 3′ untranslated sequences, and deep intronic sequences are also covered, but only known disease-causing variants in these regions will be reported. Variants identified on the panel are confirmed with Sanger sequencing if they do not meet certain quality thresholds.
Large deletions and duplications (CNVs) affecting the genes of the panel can be detected; however, due to defined settings in the analysis software, CNVs smaller than 2-kb may not be identified (for example, some small exonic level copy number changes may not be identified). Please note that certain types of genetic alterations including trinucleotide repeat expansions, methylation abnormalities, and balanced rearrangements (e.g., inversions, reciprocal translocations) may not be detected by the current analysis.
Specimen Requirements
Transport Instructions
Prenatal Transport Instructions
Connect With Our Experts
Call 1-800-473-9411 to speak with our team of laboratory genetic counselors for questions or additional information.
Robin Fletcher, MS, CGC
Falecia Thomas, MS, CGC
Alex Finley, MS, CGC