Familial intrahepatic cholestasis: New and wide perspectives.
ATP Binding Cassette Transporter, Subfamily B
/ genetics
ATP Binding Cassette Transporter, Subfamily B, Member 11
/ genetics
Adenosine Triphosphatases
/ genetics
Cholestasis, Intrahepatic
/ genetics
Disease Progression
Humans
Liver
/ physiopathology
Mutation
Receptors, Cytoplasmic and Nuclear
/ genetics
Exome Sequencing
Bioinformatics analysis
Cryptogenic disease
Genetic variants
Pathogenic mutations
Journal
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
ISSN: 1878-3562
Titre abrégé: Dig Liver Dis
Pays: Netherlands
ID NLM: 100958385
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
25
01
2019
revised:
01
04
2019
accepted:
12
04
2019
pubmed:
21
5
2019
medline:
27
2
2020
entrez:
21
5
2019
Statut:
ppublish
Résumé
Progressive familial intrahepatic cholestasis (PFIC) includes autosomal recessive cholestatic rare diseases of childhood. To update the panel of single genes mutations involved in familial cholestasis. PubMed search for "familial intrahepatic cholestasis" alone as well as in combination with other key words was performed considering primarily original studies and meta-analyses. PFIC1 involves ATP8B1 gene encoding for aminophospholipid flippase FIC1. PFIC2 includes ABCB11 gene, encoding for protein functioning as bile salt export pump. PFIC3 is due to mutations of ABCB4 gene responsible for the synthesis of class III multidrug resistance P-glycoprotein flippase. PFIC4 and PFIC5 involve tight junction protein-2 gene and NR1H4 gene encoding for farnesoid X receptor. Benign Intrahepatic Cholestasis, Intrahepatic Cholestasis of Pregnancy and Low-phospholipid-associated cholelithiasis involve the same genes and are characterized by intermittent attacks of cholestasis, no progression to cirrhosis, reversible pregnancy-specific cholestasis and cholelithiasis in young people. Blood and liver tissue levels of bile-excreted drugs can be influenced by the presence of mutations in PFIC genes, causing drug-induced cholestasis. Mutations in PFIC genes might increase the risk of liver cancer. There is a high proportion of unexplained cholestasis potentially caused by specific genetic pathophysiologic pathways. The use of next generation sequencing and whole-exome sequencing could improve the diagnostic process in this setting.
Sections du résumé
BACKGROUND
Progressive familial intrahepatic cholestasis (PFIC) includes autosomal recessive cholestatic rare diseases of childhood.
AIMS
To update the panel of single genes mutations involved in familial cholestasis.
METHODS
PubMed search for "familial intrahepatic cholestasis" alone as well as in combination with other key words was performed considering primarily original studies and meta-analyses.
RESULTS
PFIC1 involves ATP8B1 gene encoding for aminophospholipid flippase FIC1. PFIC2 includes ABCB11 gene, encoding for protein functioning as bile salt export pump. PFIC3 is due to mutations of ABCB4 gene responsible for the synthesis of class III multidrug resistance P-glycoprotein flippase. PFIC4 and PFIC5 involve tight junction protein-2 gene and NR1H4 gene encoding for farnesoid X receptor. Benign Intrahepatic Cholestasis, Intrahepatic Cholestasis of Pregnancy and Low-phospholipid-associated cholelithiasis involve the same genes and are characterized by intermittent attacks of cholestasis, no progression to cirrhosis, reversible pregnancy-specific cholestasis and cholelithiasis in young people. Blood and liver tissue levels of bile-excreted drugs can be influenced by the presence of mutations in PFIC genes, causing drug-induced cholestasis. Mutations in PFIC genes might increase the risk of liver cancer.
CONCLUSION
There is a high proportion of unexplained cholestasis potentially caused by specific genetic pathophysiologic pathways. The use of next generation sequencing and whole-exome sequencing could improve the diagnostic process in this setting.
Identifiants
pubmed: 31105019
pii: S1590-8658(19)30553-5
doi: 10.1016/j.dld.2019.04.013
pii:
doi:
Substances chimiques
ABCB11 protein, human
0
ATP Binding Cassette Transporter, Subfamily B
0
ATP Binding Cassette Transporter, Subfamily B, Member 11
0
Receptors, Cytoplasmic and Nuclear
0
farnesoid X-activated receptor
0C5V0MRU6P
multidrug resistance protein 3
9EI49ZU76O
Adenosine Triphosphatases
EC 3.6.1.-
ATP8B1 protein, human
EC 3.6.1.3.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
922-933Informations de copyright
Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.