Background: Progressive familial intrahepatic cholestasis type 2 (PFIC2) is an autosomal recessive disease due to mutations in ABCB11. ABCB11 encodes the bile salt export pump (BSEP), the major transporter responsible for biliary bile acid secretion, which expression is restricted to hepatocytes. In some patients, molecular analysis of ABCB11 revealed either exonic or intronic variations - including common polymorphisms - predicted to affect splicing according to in silico analysis or in vitro minigene studies. Transcript analysis in liver tissue is the best way to determine whether the variations predicted to affect splicing are deleterious or not.
Methods and results: We performed ABCB11 transcript analysis in liver tissue from five PFIC2 patients who had variations which were predicted to either affect splicing or not. Among eleven variants tested, only the silent c.3003A>G variant and the intronic c.3213+4A>G variant led to abnormal splicing as suggested by in silico analysis.
Conclusion: ABCB11 liver transcript analysis is a useful tool to confirm or invalidate the predicted splicing effect of a silent or intronic ABCB11 variation.
Keywords: ABCB11 gene; Aberrant splicing; BSEP; Progressive familial intrahepatic cholestasis type 2; Synonymous mutation.
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