Intrahepatic biliary anomalies in a patient with Mowat-Wilson syndrome uncover a role for the zinc finger homeobox gene zfhx1b in vertebrate biliary development

Background: zfhz1b is the causative gene for Mowat-Wilson syndrome, in which patients demonstrate developmental delay and Hirschsprung disease, as well as other anomalies.

Materials and 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.