Details of Disease

General Information of Disease (ID: DISU0AJE)

• Disease Name: Progressive familial intrahepatic cholestasis type 1
• Synonyms: Byler's disease; cholestasis, fatal intrahepatic; severe ATP8B1 deficiency; cholestasis, progressive familial intrahepatic, 1; progressive familial intrahepatic cholestasis; PFIC1; Byler disease; FIC1 deficiency; cholestasis, progressive familial intrahepatic, type 1; cholestasis, progressive familial intrahepatic 1
• Definition: PFIC1, a type of progressive familial intrahepathic cholestasis (PFIC), is an infantile hereditary disorder in bile formation that is hepatocellular in origin and associated with extrahepatic features.
• Disease Hierarchy:
  DIS3J8HT: Progressive familial intrahepatic cholestasis
  DISU0AJE: Progressive familial intrahepatic cholestasis type 1
• Disease Identifiers:
  MONDO ID: MONDO_0008892
  MESH ID: C535933
  UMLS CUI: C4551898
  OMIM ID: 211600
  MedGen ID: 1645830
  Orphanet ID: 79306
  SNOMED CT ID: 1155913007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ABCC4	TTUEAFL	Limited	Genetic Variation	[1]
SLC10A2	TTPI1M5	Limited	Biomarker	[2]
ABCB11	TTUXCAF	Strong	Genetic Variation	[3]
ABCB4	TTJUXV6	Strong	Biomarker	[4]
GGT1	TTZVT7O	Strong	Altered Expression	[5]
NR1H4	TTS4UGC	Strong	Biomarker	[6]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A13	DTDSYAQ	Strong	Genetic Variation	[7]

This Disease Is Related to 9 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ATP11C	OTKMV2K5	Limited	Genetic Variation	[8]
TJP2	OTQUY6BV	Limited	Genetic Variation	[9]
MYO5B	OTCKL3W3	Supportive	Autosomal recessive	[10]
GGTLC1	OTWJKUHQ	Strong	Altered Expression	[11]
HSD3B7	OT2Y9IW4	Strong	Genetic Variation	[12]
IMMT	OTBDSLE7	Strong	Genetic Variation	[13]
SCN7A	OTK05PXY	Strong	Biomarker	[14]
TMEM30A	OTR6N5J2	Strong	Genetic Variation	[15]
ATP8B1	OTALGS63	Definitive	Autosomal recessive	[16]

References

• [1] MDR3 (ABCB4) defects: a paradigm for the genetics of adult cholestatic syndromes.Semin Liver Dis. 2007 Feb;27(1):77-98. doi: 10.1055/s-2006-960172.
• [2] The lipid flippase heterodimer ATP8B1-CDC50A is essential for surface expression of the apical sodium-dependent bile acid transporter (SLC10A2/ASBT) in intestinal Caco-2 cells.Biochim Biophys Acta. 2014 Dec;1842(12 Pt A):2378-86. doi: 10.1016/j.bbadis.2014.09.003. Epub 2014 Sep 16.
• [3] Drugs and hepatic transporters: A review.Pharmacol Res. 2020 Apr;154:104234. doi: 10.1016/j.phrs.2019.04.018. Epub 2019 Apr 17.
• [4] ABCB4 disease: Many faces of one gene deficiency.Ann Hepatol. 2020 Mar-Apr;19(2):126-133. doi: 10.1016/j.aohep.2019.09.010. Epub 2019 Oct 31.
• [5] -Glutamyl transpeptidase level as a screening marker among diverse etiologies of infantile intrahepatic cholestasis.J Pediatr Gastroenterol Nutr. 2014 Dec;59(6):695-701. doi: 10.1097/MPG.0000000000000538.
• [6] Jaundice revisited: recent advances in the diagnosis and treatment of inherited cholestatic liver diseases.J Biomed Sci. 2018 Oct 26;25(1):75. doi: 10.1186/s12929-018-0475-8.
• [7] Utility of oligonucleotide array-based comparative genomic hybridization for detection of target gene deletions.Clin Chem. 2008 Jul;54(7):1141-8. doi: 10.1373/clinchem.2008.103721. Epub 2008 May 16.
• [8] Hepatic Tmem30a Deficiency Causes Intrahepatic Cholestasis by Impairing Expression and Localization of Bile Salt Transporters.Am J Pathol. 2017 Dec;187(12):2775-2787. doi: 10.1016/j.ajpath.2017.08.011. Epub 2017 Sep 15.
• [9] Novel compound heterozygote mutations of TJP2 in a Chinese child with progressive cholestatic liver disease.BMC Med Genet. 2019 Jan 18;20(1):18. doi: 10.1186/s12881-019-0753-7.
• [10] MYO5B mutations cause cholestasis with normal serum gamma-glutamyl transferase activity in children without microvillous inclusion disease. Hepatology. 2017 Jan;65(1):164-173. doi: 10.1002/hep.28779. Epub 2016 Oct 5.
• [11] Comorbidity between progressive familial intrahepatic cholestasis and atopic dermatitis in a 19-month-old child.BMJ Case Rep. 2019 Oct 18;12(10):e230152. doi: 10.1136/bcr-2019-230152.
• [12] Cryptogenic cholestasis in young and adults: ATP8B1, ABCB11, ABCB4, and TJP2 gene variants analysis by high-throughput sequencing.J Gastroenterol. 2018 Aug;53(8):945-958. doi: 10.1007/s00535-017-1423-1. Epub 2017 Dec 13.
• [13] A Molecular Mechanism Underlying Genotype-Specific Intrahepatic Cholestasis Resulting From MYO5B Mutations.Hepatology. 2020 Jul;72(1):213-229. doi: 10.1002/hep.31002. Epub 2020 Apr 23.
• [14] Plasma endothelin-1 levels of children with cirrhosis.J Pediatr Gastroenterol Nutr. 1995 Aug;21(2):220-3. doi: 10.1097/00005176-199508000-00015.
• [15] Differential effects of progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1 mutations on canalicular localization of ATP8B1.Hepatology. 2009 Nov;50(5):1597-605. doi: 10.1002/hep.23158.
• [16] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.