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Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
For the benefit of patients.

IllnessCholestasis, intrahepatic, pregnancy; differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for intrahepatic cholestasis during pregnancy comprising or altogether 38 curated genes according to the clinical signs

ID
CP0270
Number of genes
37 Accredited laboratory test
Examined sequence length
20,7 kb (Core-/Core-canditate-Genes)
81,7 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-GHeredity
ABCB113966AR
ABCB43840AR
ABCC24638AR
ATP8B13756AR
NR1H41419AR
TJP23063AR
AKR1D1858AR
ALDOB1095AR
AMACR1185AR
BAAT1257AR
BCS1L1260AR
CC2D2A4863AR
CLDN1636AR
CYP27A11596AR
CYP7A11515AR
CYP7B11521AR
DCDC21431AR
EPHX11368AR
FAH1260AR
HSD3B7591AR
JAG13657AD
MYO5B5547AR
NPC13837AR
NPC2456AR
PEX13852AR
PEX121080AR
PEX26918AR
PEX62943AR
RPGRIP1L3948AR
SERPINA11257AR
SLC25A132031AR
SLC27A52073AR
TALDO11014AR
TMEM672988AR
UGT1A11602AR
VIPAS391482AR
VPS33B1854AR

Informations about the disease

Clinical Comment

In intrahepatic cholestasis in pregnancy, the release of bile from liver cells is impaired, usually accompanied by itching and possibly slight icterus in the third trimester. Bile flow returns to normal after delivery, but symptoms may recur in subsequent pregnancies. Cholestasis can lead to problems in pregnancy (fetal distress, premature or even stillbirth) and affects 1% of women in (Northern) Europe. Genetic alterations in the ABCB11 or ABCB4 gene may increase a woman's likelihood of developing intrahepatic cholestasis in pregnancy. The ABCB11 gene codes for a bile salt export pump. Alterations in the ABCB11 gene associated with increased estrogen and progesterone levels decrease the function of this pump. The ABCB4 gene encodes a protein that transports phospholipids into the bile. Most women with intrahepatic cholestasis in pregnancy do not have genetic variants in the ABCB11 or ABCB4 genes. Other genetic and environmental factors probably play a role in susceptibility to the disorder, which is inherited in an autosomal dominant manner with reduced penetrance. The DNA diagnostic yield is largely unknown.

Reference: -

 

Synonyms
  • Alias: Byler disease
  • Alias: [Progressive] Familial intrahepatic cholestasis, PFIC
  • Allelic: Alpha-methylacyl-CoA racemase deficiency (AMAKR)
  • Allelic: Bardet-Biedl syndrome 14, modifier of (TMEM67)
  • Allelic: Bilirubin, serum level of, QTL1 (UGT1A1)
  • Allelic: Bjornstad syndrome (BCS1L)
  • Allelic: Citrullinemia, adult-onset type II (SLC25A13)
  • 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: Hemorrhagic diathesis due to antithrombin Pittsburgh (SERPINA1)
  • Allelic: Joubert syndrome 6 (TMEM87)
  • Allelic: Joubert syndrome 7 (RPGRIP1L)
  • Allelic: Joubert syndrome 9 (CC2D2A)
  • Allelic: Mitochondrial complex III deficiency, nuclear type 1 (BCS1L)
  • Allelic: Peroxisome biogenesis disorder 1B [NALD/IRD] (PEX1))
  • Allelic: Peroxisome biogenesis disorder 3B (PEX12)
  • Allelic: Peroxisome biogenesis disorder 4B (PEX6)
  • Allelic: Peroxisome biogenesis disorder 7B (PEX26)
  • Allelic: RHYNS syndrome (TMEM67)
  • Allelic: Spastic paraplegia 5A, AR (CYP7B1)
  • Allelic: Tetralogy of Fallot (JAG1)
  • Alagille syndrome 1 (JAG1)
  • Alagille syndrome 2 (NOTCH2)
  • Arthrogryposis, renal dysfunction + cholestasis 1 (VPS33B)
  • Arthrogryposis, renal dysfunction + cholestasis 2 (VIPAS39)
  • Bile acid synthesis defect, congenital, 1 (HSD3B7)
  • Bile acid synthesis defect, congenital, 2 (AKR1D1)
  • Bile acid synthesis defect, congenital, 3 (CYP7B1)
  • Bile acid synthesis defect, congenital, 4 (AMACR)
  • COACH syndrome 1 (TMEM67)
  • COACH syndrome 2 (CC2D2A)
  • COACH syndrome 3 (RPGRIP1L)
  • Cerebrotendinous xanthomatosis (CYP27A1)
  • Cholestasis, benign recurrent intrahepatic, 2; Cholestasis, progr. fam. intrahep. 2 (ABCB11)
  • Cholestasis, intrahepatic, of pregnancy, 1 (ATP8B1)
  • Cholestasis, intrahepatic, of pregnancy; Cholestasis, progressive fam. intrahepatic 3 (ABCB4)
  • Cholestasis, progressive familial intrahepatic 1; Cholestasis, benign recurrent intrahepatic ()
  • Cholestasis, progressive familial intrahepatic 4 (TJP2)
  • Cholestasis, progressive familial intrahepatic 5 (NR1H4)
  • Citrullinemia, type II, neonatal-onset (SLC25A13)
  • Crigler-Najjar syndrome, type I (UGT1A1)
  • Crigler-Najjar syndrome, type II (UGT1A1)
  • Deafness, congenital heart defects + posterior embryotoxon (JAG1)
  • Dubin-Johnson syndrome (ABCC2)
  • Emphysema-cirrhosis, due to AAT deficiency (SERPINA1)
  • Fructose intolerance, hereditary (ALDOB)
  • GRACILE syndrome (BCS1L)
  • Gilbert syndrome (UGT1A1)
  • Hyperbilirubinemia, familial transient neonatal (UGT1A1)
  • Hypercholanemia, familial (BAAT)
  • Hypercholanemia, familial (EPHX1)
  • Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (CLDN1)
  • Meckel syndrome 3 (TMEM67)
  • Meckel syndrome 5 (RPGRIP1L)
  • Meckel syndrome 6 (CC2D2A)
  • Microvillus inclusion disease (MYO5B)
  • Nephronophthisis 11 (TMEM67)
  • Nephronophthisis 19 (DCDC2)
  • Niemann-Pick disease, type C1 (NPC1)
  • Niemann-Pick disease, type D (NPC1)
  • Niemann-pick disease, type C2 (NPC2)
  • Peroxisome biogenesis disorder 1A [Zellweger] (PEX1)
  • Peroxisome biogenesis disorder 3A (Zellweger] (PEX12)
  • Peroxisome biogenesis disorder 4A (Zellweger] (PEX6)
  • Peroxisome biogenesis disorder 7A [Zellweger] (PEX26)
  • Sclerosing cholangitis, neonatal (DCDC2)
  • Transaldolase deficiency (TALDO)
  • Tyrosinemia, type I (FAH)
Heredity, heredity patterns etc.
  • AD
  • AR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code
O26.60

Bioinformatics and clinical interpretation

No text defined