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. Aim: 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.
- ABCB4 gene mutations
ASJC Scopus subject areas