title: Intrahepatic biliary anomalies in a patient with Mowat-Wilson syndrome uncover a role for the zinc finger homeobox gene zfhx1b in vertebrate biliary development.
abstract: BACKGROUND
  zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.
  
  
  METHODS
  We identified a patient with Mowat-Wilson syndrome who also developed cholestasis and histopathologic features consistent with biliary atresia, suggesting that mutations involving zfhz1b may lead to biliary developmental anomalies or injury to the biliary tract. We used the zebrafish model system to determine whether zfhx1b has a role in vertebrate biliary development.
  
  
  RESULTS
  Using zebrafish we determined that zfhx1b was expressed in the developing liver during biliary growth and remodeling, and that morpholino antisense oligonucleotide-mediated knockdown of zfhx1b led to defects in biliary development. These findings were associated with decreased expression of vhnf1, a transcription factor known to be important in biliary development in zebrafish and in mammals.
  
  
  CONCLUSIONS
  Our studies underscore the importance of genetic contributions in the etiology of infantile hepatobiliary disorders, including biliary atresia.
authors.affiliation: The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA 19104, USA.
authors.forename: Shuang
authors.initials: S
authors.lastname: Cui
authors.forename: Jessi
authors.initials: J
authors.lastname: Erlichman
authors.forename: Pierre
authors.initials: P
authors.lastname: Russo
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Haber
authors.forename: Randolph P
authors.initials: RP
authors.lastname: Matthews
mesh_terms: D000818:Animals; D001656:Biliary Atresia / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D001659:Biliary Tract / Q000002:abnormalities / Q000254:growth & development*; D019066:Facies; D005801:Genes, Homeobox; D051539:Hepatocyte Nuclear Factor 1-beta / Q000378:metabolism; D006627:Hirschsprung Disease / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008831:Microcephaly / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish; D000074165:Zinc Finger E-box Binding Homeobox 2; D016335:Zinc Fingers
chemical_list: C496495:HNF1B protein, human; D018398:Homeodomain Proteins; D020320:Oligoribonucleotides, Antisense; D012097:Repressor Proteins; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D051539:Hepatocyte Nuclear Factor 1-beta