AUTHOR=Lipiński Patryk , Ciara Elżbieta , Jurkiewicz Dorota , Pollak Agnieszka , Wypchło Maria , Płoski Rafał , Cielecka-Kuszyk Joanna , Socha Piotr , Pawłowska Joanna , Jankowska Irena 

TITLE=Targeted Next-Generation Sequencing in Diagnostic Approach to Monogenic Cholestatic Liver Disorders—Single-Center Experience

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 8 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2020.00414

DOI=10.3389/fped.2020.00414

ISSN=2296-2360

ABSTRACT=Objectives: To evaluate the clinical utility of panel-based next-generation sequencing (NGS) in diagnostic approach of monogenic cholestatic liver diseases.
Methods: 22 patients with diagnosis of chronic cholestatic liver disease of an unknown etiology underwent NGS of targeted genes panel including 53 items related to cholestatic liver disorders. Group 1 included 5 patients, prospectively recruited, and hospitalized from January to December 2017, while group 2 included 17 patients, retrospectively recruited, and hospitalized from 2010 to 2017 with diagnosis of low gamma-glutamyl transferase (low-GGT) progressive familial intrahepatic cholestasis (PFIC) phenotype (group 2a, 11 patients) or indeterminant cholestatic liver cirrhosis (group 2b, 6 patients).
Results: Among 22 patients enrolled into the study, 21 various pathogenic variants (including 11 novel) in 5 different genes (including ABCB11, ABCB4, TJP2, DGUOK, CYP27A1) were identified. The molecular confirmation was obtained in 15 out of 22 patients (68%).
Conclusions: Panel-based NGS appears to be a very useful tool in diagnosis of monogenic cholestatic liver disorders when extrahepatic causes have been primarily excluded. NGS presented the highest diagnosis rate to identify the molecular background of cholestatic liver diseases presenting with a low-GGT PFIC phenotype.