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

Overview

Journal Front Pediatr

Specialty Pediatrics

Date 2020 Aug 15

PMID 32793533

Citations 10

Authors

Patryk Lipinski

Elzbieta Ciara

Dorota Jurkiewicz

Agnieszka Pollak

Maria Wypchlo

Rafal Ploski

Joanna Cielecka-Kuszyk

Piotr Socha

Joanna Pawlowska

Irena Jankowska

Affiliations

Soon will be listed here.

Abstract

To evaluate the clinical utility of panel-based NGS in the diagnostic approach of monogenic cholestatic liver diseases. Patients with diagnosis of chronic cholestatic liver disease of an unknown etiology underwent NGS of targeted genes panel. Group 1 included five patients (prospectively recruited) hospitalized from January to December 2017 while group 2 included seventeen patients (retrospectively recruited) hospitalized from 2010 to 2017 presenting with low-GGT PFIC phenotype (group 2a, 11 patients) or indeterminant cholestatic liver cirrhosis (group 2b, 6 patients). Among 22 patients enrolled into the study, 21 various pathogenic variants (including 11 novel) in 5 different genes (including ) were identified. The molecular confirmation was obtained in 15 out of 22 patients (68%). In group 1, two out of five patients presented with low-GGT cholestasis, and were diagnosed with BSEP deficiency. Out of three patients presenting with high-GGT cholestasis, one patient was diagnosed with PFIC-3, and the remaining two were not molecularly diagnosed. In group 2a, seven out of eleven patients, were diagnosed with BSEP deficiency and two with TJP-2 deficiency. In group 2b, three out of six patients were molecularly diagnosed; one with PFIC-3, one with CYP27A1 deficiency, and one with DGUOK deficiency. Panel-based NGS appears to be a very useful tool in diagnosis of monogenic cholestatic liver disorders in cases 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.

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