title: Two novel mutations in African and Asian children with progressive familial intrahepatic cholestasis type 3.
abstract: BACKGROUND
  Defects in ABCB4 have been found to cause progressive familial intrahepatic cholestasis type 3. Liver histology is important, but not specific, for diagnosis. Genotyping is conclusive.
  
  
  OBJECTIVE
  To determine the pathogenetic role of two novel ABCB4 mutations in two unrelated children from North Africa and South Asia.
  
  
  METHODS
  In both children liver histology showed extensive ductular reaction with portal and periportal fibrosis. Immunohistochemical analysis displayed absence of MDR3 protein expression at the canalicular pole. Genotype analysis was performed.
  
  
  RESULTS
  Genotyping revealed two novel mutations in ABCB4: the c.1783 C>T (p.R595X) mutation in exon 15 was detected in compound heterozygosity with the c.937_992 in/del in exon 9 in one case, whereas the homozygous p.R595X mutation was recognized in the second child.
  
  
  CONCLUSIONS
  Two novel loss-of-function mutations have been identified. Progressive familial intrahepatic cholestasis type 3 has a worldwide distribution and genetic analyses are conclusive for correct diagnosis.
authors.affiliation: Dep. Pathology, Children's Hospital Bambino Gesù, Rome, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Giovannoni
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Manila
authors.initials: M
authors.lastname: Candusso
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bellacchio
authors.forename: Francesco
authors.initials: F
authors.lastname: Callea
authors.forename: Paola
authors.initials: P
authors.lastname: Francalanci
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000172:deficiency; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D010154:Pakistan; D016133:Polymerase Chain Reaction; D014416:Tunisia
chemical_list: C489273:ABCD4 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D004247:DNA