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

Objective: To evaluate the clinical utility of panel-based NGS in the diagnostic approach of monogenic cholestatic liver diseases. Study design: Patients with diagnosis of chronic cholestatic liver disease of an unknown etiology underwent NGS of targeted genes panel. Group 1 included five patients (...

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Autores principales: Lipiński, Patryk, Ciara, Elżbieta, Jurkiewicz, Dorota, Pollak, Agnieszka, Wypchło, Maria, Płoski, Rafał, Cielecka-Kuszyk, Joanna, Socha, Piotr, Pawłowska, Joanna, Jankowska, Irena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393978/
https://www.ncbi.nlm.nih.gov/pubmed/32793533
http://dx.doi.org/10.3389/fped.2020.00414
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author Lipiński, Patryk
Ciara, Elżbieta
Jurkiewicz, Dorota
Pollak, Agnieszka
Wypchło, Maria
Płoski, Rafał
Cielecka-Kuszyk, Joanna
Socha, Piotr
Pawłowska, Joanna
Jankowska, Irena
author_facet Lipiński, Patryk
Ciara, Elżbieta
Jurkiewicz, Dorota
Pollak, Agnieszka
Wypchło, Maria
Płoski, Rafał
Cielecka-Kuszyk, Joanna
Socha, Piotr
Pawłowska, Joanna
Jankowska, Irena
author_sort Lipiński, Patryk
collection PubMed
description Objective: To evaluate the clinical utility of panel-based NGS in the diagnostic approach of monogenic cholestatic liver diseases. Study design: 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). 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%). 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. Conclusions: 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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spelling pubmed-73939782020-08-12 Targeted Next-Generation Sequencing in Diagnostic Approach to Monogenic Cholestatic Liver Disorders—Single-Center Experience Lipiński, Patryk Ciara, Elżbieta Jurkiewicz, Dorota Pollak, Agnieszka Wypchło, Maria Płoski, Rafał Cielecka-Kuszyk, Joanna Socha, Piotr Pawłowska, Joanna Jankowska, Irena Front Pediatr Pediatrics Objective: To evaluate the clinical utility of panel-based NGS in the diagnostic approach of monogenic cholestatic liver diseases. Study design: 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). 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%). 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. Conclusions: 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. Frontiers Media S.A. 2020-07-24 /pmc/articles/PMC7393978/ /pubmed/32793533 http://dx.doi.org/10.3389/fped.2020.00414 Text en Copyright © 2020 Lipiński, Ciara, Jurkiewicz, Pollak, Wypchło, Płoski, Cielecka-Kuszyk, Socha, Pawłowska and Jankowska. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Lipiński, Patryk
Ciara, Elżbieta
Jurkiewicz, Dorota
Pollak, Agnieszka
Wypchło, Maria
Płoski, Rafał
Cielecka-Kuszyk, Joanna
Socha, Piotr
Pawłowska, Joanna
Jankowska, Irena
Targeted Next-Generation Sequencing in Diagnostic Approach to Monogenic Cholestatic Liver Disorders—Single-Center Experience
title Targeted Next-Generation Sequencing in Diagnostic Approach to Monogenic Cholestatic Liver Disorders—Single-Center Experience
title_full Targeted Next-Generation Sequencing in Diagnostic Approach to Monogenic Cholestatic Liver Disorders—Single-Center Experience
title_fullStr Targeted Next-Generation Sequencing in Diagnostic Approach to Monogenic Cholestatic Liver Disorders—Single-Center Experience
title_full_unstemmed Targeted Next-Generation Sequencing in Diagnostic Approach to Monogenic Cholestatic Liver Disorders—Single-Center Experience
title_short Targeted Next-Generation Sequencing in Diagnostic Approach to Monogenic Cholestatic Liver Disorders—Single-Center Experience
title_sort targeted next-generation sequencing in diagnostic approach to monogenic cholestatic liver disorders—single-center experience
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393978/
https://www.ncbi.nlm.nih.gov/pubmed/32793533
http://dx.doi.org/10.3389/fped.2020.00414
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