title: Liver transcript analysis reveals aberrant splicing due to silent and intronic variations in the ABCB11 gene.
abstract: BACKGROUND
  Progressive familial intrahepatic cholestasis type 2 (PFIC2) is an autosomal recessive disease due to mutations in ABCB11. ABCB11 encodes the bile salt export pump (BSEP), the major transporter responsible for biliary bile acid secretion, which expression is restricted to hepatocytes. In some patients, molecular analysis of ABCB11 revealed either exonic or intronic variations - including common polymorphisms - predicted to affect splicing according to in silico analysis or in vitro minigene studies. Transcript analysis in liver tissue is the best way to determine whether the variations predicted to affect splicing are deleterious or not.
  
  
  RESULTS
  We performed ABCB11 transcript analysis in liver tissue from five PFIC2 patients who had variations which were predicted to either affect splicing or not. Among eleven variants tested, only the silent c.3003A>G variant and the intronic c.3213+4A>G variant led to abnormal splicing as suggested by in silico analysis.
  
  
  CONCLUSIONS
  ABCB11 liver transcript analysis is a useful tool to confirm or invalidate the predicted splicing effect of a silent or intronic ABCB11 variation.
authors.affiliation: Biochemistry laboratory, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Sud 11, Le Kremlin-Bicêtre, France. Electronic address: anne.spraul@bct.aphp.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Davit-Spraul
authors.affiliation: Biochemistry laboratory, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Sud 11, Le Kremlin-Bicêtre, France. Electronic address: christophe.oliveira@bct.aphp.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Oliveira
authors.affiliation: Pediatric Hepatology and Liver Transplantation Unit, Hôpital Bicêtre, Reference centre for pediatric liver diseases - DHU Hepatinov, Assistance Publique - Hôpitaux de Paris, Université Paris Sud 11, Le Kremlin-Bicêtre, France; INSERM U757, University Paris-Sud 11, Orsay, France. Electronic address: emmanuel.gonzales@bct.aphp.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gonzales
authors.affiliation: Biochemistry laboratory, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Sud 11, Le Kremlin-Bicêtre, France. Electronic address: pauline.gaignard@bct.aphp.fr.
authors.forename: Pauline
authors.initials: P
authors.lastname: Gaignard
authors.affiliation: Biochemistry laboratory, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Sud 11, Le Kremlin-Bicêtre, France. Electronic address: patrice.therond@bct.aphp.fr.
authors.forename: Patrice
authors.initials: P
authors.lastname: Thérond
authors.affiliation: Pediatric Hepatology and Liver Transplantation Unit, Hôpital Bicêtre, Reference centre for pediatric liver diseases - DHU Hepatinov, Assistance Publique - Hôpitaux de Paris, Université Paris Sud 11, Le Kremlin-Bicêtre, France; INSERM U757, University Paris-Sud 11, Orsay, France. Electronic address: emmanuel.jacquemin@bct.aphp.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jacquemin
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D002780:Cholestasis, Intrahepatic / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D056726:Genetic Association Studies; D006801:Humans; D007438:Introns; D008099:Liver / Q000378:metabolism*; D020125:Mutation, Missense; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D020033:Protein Isoforms; D022821:RNA Splice Sites; D012333:RNA, Messenger
keywords: ABCB11 gene; Aberrant splicing; BSEP; Progressive familial intrahepatic cholestasis type 2; Synonymous mutation