Resumen

Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive cholestatic diseases of child-hood and represents the main indication for liver transplantation at this age; PFIC2 involves ABCB11 gene, that encodes the ATP-dependent canalicular bile salt export pump (BSEP). Benign intrahepatic cholestasis (BRIC) identifies a group of diseases involving the same genes and characterized by intermittent attacks of cholestasis with no progression to liver cirrhosis. Diagnosis with standard sequencing techniques is expensive and available only at a few tertiary centers. We report the application of next generation se-quencing (NGS) in the diagnosis of the familial intrahepatic cholestasis with a parallel sequencing of three causative genes. We identified the molecular defects in ABCB11 gene in two different probands who developed a severe cholestatic disease of unknown origin. In the first patient a compound heterozygosity for the novel frame shift mutation p.Ser1100GlnfsX38 and the missense variantp.Glu135Lys was detected. In the second patient, triggered by contraceptive therapy, we identified homozygosity for a novel missense variant p.Ala523Gly. In conclusion, these mutations seem to have a late onset and a less aggressive clinical impact, actingas an intermediate form between BRIC and PFIC.

Palabras clave: Progressive familial intrahepatic cholestasis benign intrahepatic cholestasis cholestatic diseases gamma-glutamil-transpeptidase alkaline phosphatase.

2016-10-21   |   263 visitas   |   Evalua este artículo 0 valoraciones

Vol. 15 Núm.5. Septiembre-Octubre 2016 Pags. 795-800 Ann Hepatol 2016; 15(5)