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Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
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IllnessCholestasis, congenital + adult; differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for congenital/adult cholestasis comprising 20 guideline-curated genes and altogether 75 curated genes according to the clinical signs

ID
CP5599
Number of genes
51 Accredited laboratory test
Examined sequence length
47,6 kb (Core-/Core-canditate-Genes)
128,0 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

[Sanger]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
ABCB113966NM_003742.4AR
ABCB43840NM_000443.4AR
AKR1D1858NM_001190906.2AR
ATP8B13756NM_005603.6AR
BAAT1257NM_001127610.2AR
CFTR4443NM_000492.4AR
CLDN1636NM_021101.5AR
FAH1260NM_000137.4AR
GALT1140NM_000155.4AR
HSD3B7591NM_001142777.2AR
JAG13657NM_000214.3AD
LIPA1200NM_000235.4AR
NOTCH27416NM_024408.4AD
NPC13837NM_000271.5AR
SERPINA11257NM_000295.5AR
SLC25A132031NM_001160210.2AR
TJP23063NM_004817.4AR
VIPAS391482NM_022067.4AR
VPS33B1854NM_018668.5AR
ABCC24638NM_000392.5AR
ALDOB1095NM_000035.4AR
AMACR1185NM_001167595.2AR
ATP7B4398NM_000053.4AR
BCS1L1260NM_004328.5AR
CC2D2A4863NM_001080522.2AR
CYP27A11596NM_000784.4AR
CYP7B11521NM_004820.5AR
DCDC21431NM_016356.5AR
DGUOK834NM_080916.3AR
HNF1B1674NM_000458.4AD
INVS3198NM_014425.5AR
MKS11680NM_017777.4AR
MPV17531NM_002437.5AR
MVK1191NM_000431.4AR
MYO5B5547NM_001080467.3AR
NPC2456NM_006432.5AR
NPHP33993NM_153240.5AR
NR1H41419NM_005123.4AR
PEX13852NM_000466.3AR
PEX121080NM_000286.3AR
PEX26918NM_017929.6AR
PEX62943NM_000287.4AR
PKHD112225NM_138694.4AR
POLG3720NM_002693.3AR
RPGRIP1L3948NM_015272.5AR
SMPD11896NM_000543.5AR
TALDO11014NM_006755.2AR
TMEM216438NM_001173990.3AR
TMEM672988NM_153704.6AR
TRMU1266NM_018006.5AR
UGT1A11602NM_000463.3AR

Informations about the disease

Clinical Comment

Cholestasis is defined as a decrease in bile flow due to impaired secretion by hepatocytes or obstruction of bile flow by intra- or extrahepatic bile ducts. The clinical definition of cholestasis is any condition in which substances normally secreted into the bile are retained. The mechanisms of cholestasis can be broadly divided into hepatocellular, in which impairment of bile formation occurs, and obstructive, in which obstruction of bile flow occurs after its formation. Accumulation of bile acids leads to pruritus, hepatocyte toxicity, and cirrhosis. Neonatal cholestasis includes a variety of different disorders, several of which are caused monogenically. Progressive familial intrahepatic cholestasis accounts for more than 15% of neonatal cholestasis syndromes and approximately 15% of liver transplants in childhood. Using a large targeted gene panel for infants with cholestasis after exclusion of biliary atresia, more than 80% of infants received a diagnosis of monogenic etiology. Although affected individuals typically develop liver failure before adulthood, cases with later onset can be differentiated by comprehensive DNA studies. Most monogenic cholestatic disorders are inherited in an autosomal recessive manner. DNA diagnostic yield, by its very nature, depends critically on prior clinical case workup. But a negative molecular genetic result does not constitute exclusion of the clinical diagnosis.

Reference: https://doi.org/10.1002/cld.872

 

Synonyms
  • Allelic: Bardet-Biedl syndrome 14, modifier of (TMEM67)
  • Allelic: Bjornstad syndrome (BCS1L)
  • Allelic: Bronchiectasis with or without elevated sweat chloride 1, modifier of (CFTR)
  • Allelic: Bronchiectasis with/-out elevated sweat chloride 1, modifier of (CFTR)
  • Allelic: Charcot-Marie-Tooth disease, DI C (YARS1)
  • Allelic: Congenital bilateral absence of vas deferens (CFTR)
  • Allelic: Deafness, AR 66 (DCDC2)
  • Allelic: Deafness, congenital heart defects + posterior embryotoxon (JAG1)
  • Allelic: Emphysema due to AAT deficiency (SERPINA1)
  • Allelic: Hajdu-Cheney syndrome (NOTCH2)
  • Allelic: Heimler syndrome 1 (PEX1)
  • Allelic: Heimler syndrome 2 (PEX6)
  • Allelic: Hyper-IgD syndrome (MVK)
  • Allelic: Hypertrypsinemia, neonatal (CFTR)
  • Allelic: Joubert syndrome 28 (MKS1)
  • Allelic: Joubert syndrome 6 (TMEM67)
  • Allelic: Joubert syndrome 7 (RPGRIP1L)
  • Allelic: Joubert syndrome 9 (CC2D2A)
  • Allelic: Lewy body dementia, susceptibility to (GBA1)
  • Allelic: Meckel syndrome 1 (MKS1)
  • Allelic: Meckel syndrome 3 (TMEM67)
  • Allelic: Meckel syndrome 5 (RPGRIP1L)
  • Allelic: Meckel syndrome 6 (CC2D2A)
  • Allelic: Nephronophthisis 11 (TMEM67)
  • Allelic: Nephronophthisis 19 (DCDC2)
  • Allelic: Pancreatitis, hereditary (CFTR)
  • Allelic: Parkinson disease, late-onset, susceptibility to (GBA1)
  • Allelic: Perrault syndrome 1 (HSD17B4)
  • Allelic: Porokeratosis 3, multiple types (MVK)
  • Allelic: Progressive external ophthalmoplegia with mtDNA deletions, AR 4 (DGUOK)
  • Allelic: RHYNS syndrome (TMEM67)
  • Allelic: Renal cell carcinoma (HNF1B)
  • Allelic: Short stature, optic nerve atrophy + Pelger-Huet anomaly (NBAS)
  • Allelic: Spastic paraplegia 5A, AR (CYP7B1)
  • Allelic: Sweat chloride elevation without CF (CFTR)
  • Allelic: Tetralogy of Fallot (JAG1)
  • Allelic: Type 2 diabetes mellitus (HNF1B)
  • Renal cysts + diabetes syndrome (HNF1B)
  • Acute liver failure, included
  • Alagille syndrome 1 (JAG1)
  • Alagille syndrome 2 (NOTCH2)
  • Alpha-1 Antitrypsin Deficiency, included
  • Alpha-methylacyl-CoA racemase deficiency (AMACR)
  • Arthrogryposis, renal dysfunction + cholestasis 1 (VPS33B)
  • Arthrogryposis, renal dysfunction + cholestasis 2 (VIPAS39)
  • Bardet-Biedl syndrome 13 (MKS1)
  • Bile acid synthesis defect, congenital, 1 (HSD3B7)
  • Bile acid synthesis defect, congenital, 2 (AKR1D1)
  • Bile acid synthesis defect, congenital, 3 (CYP7A1, CYP7B1)
  • Bile acid synthesis defect, congenital, 4 (AMACR)
  • Bile salt synthesis defect, included
  • Bilirubin, serum level of, QTL1 (UGT1A1)
  • COACH syndrome 1 (TMEM67)
  • COACH syndrome 2 (CC2D2A)
  • COACH syndrome 3 (RPGRIP1L)
  • Cerebrotendinous xanthomatosis (CYP27A1)
  • Cholestasis, benign recurrent intrahepatic (ATP8B1)
  • Cholestasis, benign recurrent intrahepatic, 2 (ABCB11)
  • Cholestasis, included
  • Cholestasis, intrahepatic, of pregnancy, 1 (ATP8B1)
  • Cholestasis, intrahepatic, of pregnancy, 3 (ABCB4)
  • Cholestasis, progressive familial intrahepatic, 1 (ATP8B1)
  • Cholestasis, progressive familial intrahepatic, 2 (ABCB11)
  • Cholestasis, progressive familial intrahepatic, 3 (ABCB4)
  • Cholestasis, progressive familial intrahepatic, 4 (TJP2)
  • Cholestasis, progressive familial intrahepatic, 5 (NR1H4)
  • Cholestasis, progressive familial intrahepatic, 7, with/-out hearing loss (USP53)
  • Cholestasis, progressive familial intrahepatic, 8 (KIF12)
  • Cholestasis, progressive familial intrahepatic, 9 (ZFYVE19)
  • Cholesteryl ester storage disease (LIPA)
  • Citrullinemia, adult-onset type II (SLC25A13)
  • Citrullinemia, type II, neonatal-onset (SLC25A13)
  • Congenital disorder of glycosylation, type IIe (COG7)
  • Congenital disorder of glycosylation, type Ib (MPI)
  • Congenital hepatic fibrosis, included
  • Crigler-Najjar syndrome, type I (UGT1A1)
  • Crigler-Najjar syndrome, type II (UGT1A1)
  • Cystic fibrosis (CFTR)
  • D-bifunctional protein deficiency (HSD17B4)
  • Dubin-Johnson syndrome (ABCC2)
  • Emphysema-cirrhosis, due to AAT deficiency (SERPINA1)
  • Familial intrahepatic cholestasis, included
  • Fanconi renotubular syndrome 3 (EHHAADH)
  • Fat soluble vitamin deficiency, included
  • Fatty liver, acute, of pregnancy (HADHA)
  • Fructose intolerance, hereditary (ALDOB)
  • GRACILE syndrome (BCS1L)
  • Galactokinase deficiency with cataracts (GALK)
  • Galactose epimerase deficiency (GALE)
  • Galactosemia (GALT)
  • Galactosemia IV (GALM)
  • Gallbladder disease 1 (ABCB4)
  • Gallbladder disease 4 (ABCG8)
  • Gaucher disease, perinatal lethal (GBA1)
  • Gaucher disease, type I, II, III, IIIC (GBA1)
  • Gilbert syndrome (UGT1A1)
  • Glycogen storage disease IV (GBE1)
  • HELLP syndrome, maternal, of pregnancy (HADHA)
  • Hemorrhagic diathesis due to antithrombin Pittsburgh (SERPINA1)
  • Hyperbilirubinemia, familial transient neonatal (UGT1A1)
  • Hypercholanemia, familial (BAAT, TJP2)
  • Hypermethioninemia due to adenosine kinase deficiency (ADK)
  • Ichthyosis, leukocyte vacuoles, alopecia and sclerosing cholangitis (CLDN1)
  • Ichthyosis-hypotrichosis-sclerosing cholangitis, included
  • Infantile liver failure syndrome 2 (NBAS)
  • Infantile liver failure syndrome 3 (RINT1)
  • Infantile-onset multisystem neurologic, endocrine + pancreatic disease 2 (YARS1)
  • LCHAD deficiency (HADHA)
  • MYO5B associated diseas, included
  • Mevalonic aciduria (MVK)
  • Microvillus inclusion disease (MYO5B)
  • Mitochondrial DNA depletion syndrome 3 [hepatocerebral type] (DGUOK)
  • Mitochondrial complex III deficiency, nuclear type 1 (BCS1L)
  • Mitochondrial trifunctional protein deficiency (HADHA)
  • Neonatal and adult cholestasis (GPBAR1)
  • Neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome, included
  • Neonatal sclerosis cholangitis, included
  • Nephronophthisis 2, infantile (INVS)
  • Nephronophthisis, included
  • Niemann-Pick disease, type C1 (NPC1)
  • Niemann-Pick disease, type C2 (NPC2)
  • Niemann-Pick disease, type D (NPC1)
  • Ornithine transcarbamylase deficiency (OTC)
  • Osteootohepatoenteric syndrome (UNC45A)
  • Peroxisome biogenesis disorder 10A, Zellweger (PEX3)
  • Peroxisome biogenesis disorder 10B (PEX3)
  • Peroxisome biogenesis disorder 11A, Zellweger (PEX13)
  • Peroxisome biogenesis disorder 11B (PEX13)
  • Peroxisome biogenesis disorder 12A, Zellweger (PEX19)
  • Peroxisome biogenesis disorder 13A, Zellweger (PEX14)
  • Peroxisome biogenesis disorder 1A, Zellweger (PEX1)
  • Peroxisome biogenesis disorder 1B, NALD/IRD (PEX1)
  • Peroxisome biogenesis disorder 3A, Zellweger (PEX12)
  • Peroxisome biogenesis disorder 3B (PEX12)
  • Peroxisome biogenesis disorder 4A, Zellweger (PEX6)
  • Peroxisome biogenesis disorder 4B (PEX6)
  • Peroxisome biogenesis disorder 5A, Zellweger (PEX2)
  • Peroxisome biogenesis disorder 5B (PEX2)
  • Peroxisome biogenesis disorder 6A, Zellweger (PEX10)
  • Peroxisome biogenesis disorder 6B (PEX10)
  • Peroxisome biogenesis disorder 7A, Zellweger (PEX26)
  • Peroxisome biogenesis disorder 7B (PEX26)
  • Peroxisome biogenesis disorder 8A, Zellweger (PEX16)
  • Peroxisome biogenesis disorder 8B (PEX16)
  • Polyglucosan body disease, adult form (GBE1)
  • Portal hypertension, noncirrhotic (DGUOK)
  • Sclerosing cholangitis, neonatal (DCDC2)
  • Severe neonatal cholestasis, included
  • Sitosterolemia 1 (ABCG8)
  • Sitosterolemia 2 (ABCG5)
  • Smith-Lemli-Opitz syndrome (DHCR7)
  • Transaldolase deficiency (TALDO1)
  • Tyrosinaemia, type 1 (FAH)
  • Unconjugated jaundice, included
  • Wilson disease (ATP7B)
  • Wolman disease (LIPA)
Heredity, heredity patterns etc.
  • AD
  • AR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

No text defined