Lin_2023_Pancreatology_S1424-3903_01834

Reference

Title : Characterization of novel PNLIP variants in congenital pancreatic lipase deficiency - Lin_2023_Pancreatology_S1424-3903_01834
Author(s) : Lin J , Matiwala N , Curry GE , Wilhelm SJ , Cassidy BM , Lowe ME , Xiao X
Ref : Pancreatology , : , 2023
Abstract :

BACKGROUND/OBJECTIVES: Studies of a rare homozygous missense mutation identified in two brothers diagnosed with congenital pancreatic lipase deficiency (CPLD) provided the first definitive evidence linking CPLD with missense mutations in the gene of PNLIP. Herein, we investigated the molecular basis for the loss-of-function in the three novel PNLIP variants (c.305G > A, p.(W102); c.562C > T, p.(R188C); and c.1257G > A, p.(W419)) associated with CPLD. METHODS: We characterized three novel PNLIP variants in transfected cells by assessing their secretion, intracellular distribution, and markers of endoplasmic reticulum (ER) stress. RESULTS: All three variants had secretion defects. Notably, the p.R188C and p.W419 variants induced misfolding of PNLIP and accumulated as detergent-insoluble aggregates resulting in elevated BiP at both protein and mRNA levels indicating increased ER stress. CONCLUSIONS: All three novel PNLIP variants cause a loss-of-function through impaired secretion. Additionally, the p.R188C and p.W419 variants may induce proteotoxicity through misfolding and potentially increase the risk for pancreatic acinar cell injury.

PubMedSearch : Lin_2023_Pancreatology_S1424-3903_01834
PubMedID: 37926600
Gene_locus related to this paper: human-PNLIP

Citations formats

Lin J, Matiwala N, Curry GE, Wilhelm SJ, Cassidy BM, Lowe ME, Xiao X (2023)
Characterization of novel PNLIP variants in congenital pancreatic lipase deficiency
Pancreatology :

Lin J, Matiwala N, Curry GE, Wilhelm SJ, Cassidy BM, Lowe ME, Xiao X (2023)
Pancreatology :