Identification of protease-sensitive but not misfolding PNLIP variants in familial and hereditary pancreatitis

Masson, Emmanuelle, Berthet, Stéphanie, Le Gac, Gerald, Le Rhun, Marc, Ka, Chandran, Autret, Sandrine, Gourlaouen, Isabelle, Cooper, David N. ORCID: https://orcid.org/0000-0002-8943-8484, Férec, Claude, Rebours, Vinciane and Chen, Jian-Min 2023. Identification of protease-sensitive but not misfolding PNLIP variants in familial and hereditary pancreatitis. Pancreatology 23 (5) , pp. 507-511. 10.1016/j.pan.2023.05.011 Item availability restricted.

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Abstract

Mutations in the PNLIP gene have recently been implicated in chronic pancreatitis. Several PNLIP missense variants have been reported to cause protein misfolding and endoplasmic reticulum stress although genetic evidence supporting their association with chronic pancreatitis is currently lacking. Protease-sensitive PNLIP missense variants have also been associated with early-onset chronic pancreatitis although the underlying pathological mechanism remains enigmatic. Herein, we provide new evidence to support the association of protease-sensitive PNLIP variants (but not misfolding PNLIP variants) with pancreatitis. Specifically, we identified protease-sensitive PNLIP variants in 5 of 373 probands (1.3%) with a positive family history of pancreatitis. The protease-sensitive variants, p.F300L and p.I265R, were found to segregate with the disease in three families, including one exhibiting a classical autosomal dominant inheritance pattern. Consistent with previous findings, protease-sensitive variant-positive patients were often characterized by early-onset disease and invariably experienced recurrent acute pancreatitis, although none has so far developed chronic pancreatitis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/, Start Date: 2024-07-19
Publisher:	Elsevier
ISSN:	1424-3903
Date of First Compliant Deposit:	26 July 2023
Date of Acceptance:	26 May 2023
Last Modified:	17 Nov 2023 10:03
URI:	https://orca.cardiff.ac.uk/id/eprint/161248

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