Abstract
Progressive familial intrahepatic cholestasis (PFIC) syndromes are characterized by defects in transporters of conjugated bile acids into the bile canaliculus. Three genes (ATP8B1, ABCB11, ABCB4) are associated with the different forms, but no easy genotype–phenotype correlations help in the prioritization for gene testing. We developed a denaturing high-performance liquid chromatography (DHPLC) method to screen patients with PFIC for mutations in ATP8B1 and ABCB11, and combined genetic analyses with immunolabeling in liver for the ABCB11 and ABCB4 gene products. Used in combination with commercially available antibodies on liver specimens, the DHPLC approach allowed us to confirm the clinical diagnosis in two Italian sisters and to identify a novel missesnse mutation in ABCB11. Our findings are expected to facilitate detection of the molecular cause of PFIC in affected families.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
WF Balistreri JA Bezerra P Jansen SJ Karpen BL Shneider FJ Suchy (2005) ArticleTitleIntrahepatic cholestasis: summary of an American Association for the Study of Liver Diseases single-topic conference Hepatology 42 222–35 Occurrence Handle15898074 Occurrence Handle10.1002/hep.20729
MJ Harris DG Le Couteur IM Arias (2005) ArticleTitleProgressive familial intrahepatic cholestasis: genetic disorders of biliary transporters J Gastroenterol Hepatol 20 807–17 Occurrence Handle15946126 Occurrence Handle1:CAS:528:DC%2BD2MXmslCisL4%3D Occurrence Handle10.1111/j.1440-1746.2005.03743.x
SW van Mil RH Houwen LW Klomp (2005) ArticleTitleGenetics of familial intrahepatic cholestasis syndromes J Med Genet 42 449–63 Occurrence Handle15937079 Occurrence Handle1:CAS:528:DC%2BD2MXmt1CitLc%3D Occurrence Handle10.1136/jmg.2004.026187
W Xiao PJ Oefner (2001) ArticleTitleDenaturing high-performance liquid chromatography. A review Hum Mutat 17 439–74 Occurrence Handle11385705 Occurrence Handle1:CAS:528:DC%2BD3MXks1antr4%3D Occurrence Handle10.1002/humu.1130
VN Kristensen D Kelefiotis T Kristensen AL Borresen-Dale (2001) ArticleTitleHigh-throughput methods for detection of genetic variation Biotechniques 30 318–22 Occurrence Handle11233601 Occurrence Handle1:CAS:528:DC%2BD3MXhtFCmtrs%3D
ML Heritage JC MacMillan GJ Anderson (2002) ArticleTitleDHPLC mutation analysis of Jagged1 (JAG1) reveals six novel mutations in Australian Alagille syndrome patients Hum Mutat 20 481 Occurrence Handle12442286 Occurrence Handle10.1002/humu.9095
H Hayashi T Takada H Suzuki H Akita Y Sugiyama (2005) ArticleTitleTwo common PFIC2 mutations are associated with the impaired membrane trafficking of BSEP/ABCB11 Hepatology 41 916–24 Occurrence Handle15791618 Occurrence Handle1:CAS:528:DC%2BD2MXjsV2msbg%3D Occurrence Handle10.1002/hep.20627
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nobili, V., Giandomenico, S., Francalanci, P. et al. A new ABCB11 mutation in two Italian children with familial intrahepatic cholestasis. J Gastroenterol 41, 598–603 (2006). https://doi.org/10.1007/s00535-006-1816-z
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s00535-006-1816-z