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A novel frameshift mutation in TRPV6 is associated with hereditary pancreatitis

Shah, IA and Prasad, H and Banerjee, S and Kurien, RT and Chowdhury, SD and Visweswariah, SS (2023) A novel frameshift mutation in TRPV6 is associated with hereditary pancreatitis. In: Frontiers in Genetics, 13 .

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Official URL: https://doi.org/10.3389/fgene.2022.1058057


Introduction: Hereditary pancreatitis (HP) is a rare debilitating disease with incompletely understood etio-pathophysiology. The reduced penetrance of genes such as PRSS1 associated with hereditary pancreatitis indicates a role for novel inherited factors. Methods: We performed whole-exome sequencing of three affected members of an Indian family (Father, Son, and Daughter) with chronic pancreatitis and compared variants with those seen in the unaffected mother. Results: We identified a novel frameshift mutation in exon 11 of TRPV6 (c.1474_1475delGT; p.V492Tfs*136), a calcium channel, in the patients. Functional characterization of this mutant TRPV6 following heterologous expression revealed that it was defective in calcium uptake. Induction of pancreatitis in mice induced Trpv6 expression, indicating that higher expression levels of the mutant protein and consequent dysregulation of calcium levels in patients with chronic pancreatitis could aggravate the disease. Discussion: We report a novel frameshift mutation in TRPV6 in an Indian family with HP that renders the mutant protein inactive. Our results emphasize the need to expand the list of genes used currently for evaluating patients with hereditary pancreatitis.

Item Type: Journal Article
Publication: Frontiers in Genetics
Publisher: Frontiers Media S.A.
Additional Information: The copyright for this article belongs to the Authors.
Keywords: CaSR; FGF23; pancreatitis; TRPV6 (transient receptor potential cation channel subfamily V member 6); WES - whole-exome sequencing
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited: 16 Feb 2023 05:06
Last Modified: 16 Feb 2023 05:06
URI: https://eprints.iisc.ac.in/id/eprint/80298

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