Two novel mutations in African and Asian children with progressive familial intrahepatic cholestasis type 3

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish
Pages (from-to)567-570
Number of pages4
JournalDigestive and Liver Disease
Volume43
Issue number7
DOIs
Publication statusPublished - Jul 2011

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Mutation
Exons
Histology
Northern Africa
Liver
Fibrosis
Genotype
Progressive familial intrahepatic 3 Cholestasis

Keywords

  • ABCB4 gene mutations

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

@article{13f20e43459c4f7793feb9fe74927557,
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. 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.",
keywords = "ABCB4 gene mutations",
author = "Isabella Giovannoni and Santorelli, {Filippo Maria} and Manila Candusso and {Di Rocco}, Maja and Emanuele Bellacchio and Francesco Callea and Paola Francalanci",
year = "2011",
month = "7",
doi = "10.1016/j.dld.2011.03.004",
language = "English",
volume = "43",
pages = "567--570",
journal = "Digestive and Liver Disease",
issn = "1590-8658",
publisher = "Elsevier B.V.",
number = "7",

}

TY - JOUR

T1 - Two novel mutations in African and Asian children with progressive familial intrahepatic cholestasis type 3

AU - Giovannoni, Isabella

AU - Santorelli, Filippo Maria

AU - Candusso, Manila

AU - Di Rocco, Maja

AU - Bellacchio, Emanuele

AU - Callea, Francesco

AU - Francalanci, Paola

PY - 2011/7

Y1 - 2011/7

N2 - 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.

AB - 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.

KW - ABCB4 gene mutations

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