title: Bile salt export pump gene mutations in two Japanese patients with progressive familial intrahepatic cholestasis.
abstract: BACKGROUND
  In recent years, progressive familial intrahepatic cholestasis has been classified into at least three types by genetic analysis: PFIC1, PFIC2, and MDR3. Liver transplantation is effective for treating patients with this intractable syndrome. Confirming the correct diagnosis is of paramount importance because prognosis after transplantation differs with the genetic type of the disease.
  
  
  METHODS
  Synthesis of cDNA was accomplished using RNA extracted from liver tissue of two Japanese patients with progressive familial intrahepatic cholestasis. Polymerase chain reaction was performed using 13 primer sets designed for amplification of the bile salt export pump cDNA. Direct sequencing was undertaken, and identified sequences were compared with the sequence for bile salt export pump gene registered with GenBank. In addition, gene sequences for nonprogressive familial intrahepatic cholestasis patients were analyzed.
  
  
  RESULTS
  Genetic analysis of patient 1 revealed that substitutions in bile salt export pump protein sequences, namely R575X and E636G, might be the cause of the disease. In patient 2, V330X and R487H might fulfill the same role. Results of gene analysis in parents and cholestatic controls supported these conclusions.
  
  
  CONCLUSIONS
  Absence or presence of bile salt export protein gene mutations was confirmed as representing a useful prognostic marker for clinical course after liver transplantation.
authors.affiliation: Department of Peditrics, Nagoya City University Medical School, Nagoya, Japan. k_goto@med.nagoya-cu.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Goto
authors.forename: Kohachiro
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Tokio
authors.initials: T
authors.lastname: Sugiura
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Ando
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Mizutani
authors.forename: Koji
authors.initials: K
authors.lastname: Terabe
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ban
authors.forename: Hajime
authors.initials: H
authors.lastname: Togari
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002780:Cholestasis, Intrahepatic / Q000235:genetics*; D018389:Codon, Nonsense; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D018389:Codon, Nonsense; D018076:DNA, Complementary