Next generation sequencing misguided the clinical interpretation of the PRSS1 variant in pediatric pancreatitis: a case report

Next-generation sequencing (NGS), known as massively parallel sequencing, is transitioning from research tools to a clinical diagnostic methods. Whole-exome sequencing (WES), a specific applications of NGS, has emerged as a valuablefirst-line diagnostic tool for patients with rare diseases and shows...

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Main Authors: Yao Liu, Hongjun Miao, Qin Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Pediatrics
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Online Access:https://www.frontiersin.org/articles/10.3389/fped.2025.1572366/full
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author Yao Liu
Hongjun Miao
Qin Zhang
author_facet Yao Liu
Hongjun Miao
Qin Zhang
author_sort Yao Liu
collection DOAJ
description Next-generation sequencing (NGS), known as massively parallel sequencing, is transitioning from research tools to a clinical diagnostic methods. Whole-exome sequencing (WES), a specific applications of NGS, has emerged as a valuablefirst-line diagnostic tool for patients with rare diseases and shows promise as aas a comprehensive approach for assessing the prevalence of hereditary pancreatitis. Herein, we present a pediatric case that highlights the pitfalls of false-positive missense variants calls in the PRSS1 gene when using NGS. The patient was ultimately diagnosed with valproic acid-induced acute pancreatitis. Our findings emphasize that relying solely on WES data in epidemiological studies of hereditary pancreatitis might introduce bias, given the difficulties in accurately detecting variants within highly homologous genomic regions.
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publisher Frontiers Media S.A.
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spelling doaj-art-6fffefb1e0a04c73a342f48503a05ee22025-08-20T03:59:44ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602025-08-011310.3389/fped.2025.15723661572366Next generation sequencing misguided the clinical interpretation of the PRSS1 variant in pediatric pancreatitis: a case reportYao Liu0Hongjun Miao1Qin Zhang2Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Emergency, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Emergency, Children's Hospital of Nanjing Medical University, Nanjing, ChinaNext-generation sequencing (NGS), known as massively parallel sequencing, is transitioning from research tools to a clinical diagnostic methods. Whole-exome sequencing (WES), a specific applications of NGS, has emerged as a valuablefirst-line diagnostic tool for patients with rare diseases and shows promise as aas a comprehensive approach for assessing the prevalence of hereditary pancreatitis. Herein, we present a pediatric case that highlights the pitfalls of false-positive missense variants calls in the PRSS1 gene when using NGS. The patient was ultimately diagnosed with valproic acid-induced acute pancreatitis. Our findings emphasize that relying solely on WES data in epidemiological studies of hereditary pancreatitis might introduce bias, given the difficulties in accurately detecting variants within highly homologous genomic regions.https://www.frontiersin.org/articles/10.3389/fped.2025.1572366/fullPRSS1pediatricacute pancreatitisNGS - next generation sequencingpitfall
spellingShingle Yao Liu
Hongjun Miao
Qin Zhang
Next generation sequencing misguided the clinical interpretation of the PRSS1 variant in pediatric pancreatitis: a case report
Frontiers in Pediatrics
PRSS1
pediatric
acute pancreatitis
NGS - next generation sequencing
pitfall
title Next generation sequencing misguided the clinical interpretation of the PRSS1 variant in pediatric pancreatitis: a case report
title_full Next generation sequencing misguided the clinical interpretation of the PRSS1 variant in pediatric pancreatitis: a case report
title_fullStr Next generation sequencing misguided the clinical interpretation of the PRSS1 variant in pediatric pancreatitis: a case report
title_full_unstemmed Next generation sequencing misguided the clinical interpretation of the PRSS1 variant in pediatric pancreatitis: a case report
title_short Next generation sequencing misguided the clinical interpretation of the PRSS1 variant in pediatric pancreatitis: a case report
title_sort next generation sequencing misguided the clinical interpretation of the prss1 variant in pediatric pancreatitis a case report
topic PRSS1
pediatric
acute pancreatitis
NGS - next generation sequencing
pitfall
url https://www.frontiersin.org/articles/10.3389/fped.2025.1572366/full
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