Rapid communicationsBenign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11☆
Section snippets
Patients
All studies were conducted under approved protocols in accordance with the guidelines of the children’s study committee of the University Medical Center Utrecht and referring centers. All BRIC patients had been diagnosed previously on the basis of clinical symptoms in combination with routine laboratory investigations. Inclusion criteria for this study were normal γ-glutamyl transpeptidase activity in serum and no obstruction of extrahepatic bile ducts. Patients were included only when at least
BSEP mutation analysis in BRIC patients
We screened all coding exons including intron-exon boundaries of ABCB11 for mutations in patients from 20 different BRIC families in whom ATP8B1 mutations had been excluded. Apparent homozygous ABCB11 mutations were detected in 7 patients from 5 families, and 3 patients from 2 families were compound heterozygous for ABCB11 mutations. In 1 patient (family 32) we detected only one heterozygous mutation. In total, 8 distinct mutations in ABCB11 were detected in 11 patients from 8 different
Discussion
We present a subtype of BRIC caused by mutations in ABCB11, the gene encoding the hepatocellular bile salt export pump (BSEP). This description of mutations in a gene other than ATP8B1 causing autosomal recessive BRIC, is consistent with previous preliminary findings.16 Autosomal-dominant BRIC also was reported, but the causative gene mutation has not been elucidated.17 To differentiate between the 2 distinct recessive forms of BRIC, we propose to denote BRIC caused by mutations in ATP8B1 as
Acknowledgements
The authors thank the participating families and referring physicians, and Frank Lammert for helpful discussions.
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Supported by grant WS98-12 from the Dutch Digestive Disease Foundation (to L.W.J.K.), grant 2002B17 from the Dutch Heart Foundation (to E.S.), grant 902-23-191 from the Dutch Organization for Scientific Research (to P.L.M.J.), and R01 grant DK50697 from the National Institutes of Health (to L.N.B.).
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The current address for P.L.M.J. is Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands.