Afficher la notice abrégée

Functionally deficient TRPV6 variants contribute to hereditary and familial chronic pancreatitis

dc.rights.licenseopenen_US
dc.contributor.authorHAMADA, Shin
dc.contributor.authorMASSON, Emmanuelle
dc.contributor.authorCHEN, Jian Min
dc.contributor.authorSAKAGUCHI, Reiko
dc.contributor.authorREBOURS, Vinciane
dc.contributor.authorBUSCAIL, Louis
dc.contributor.authorMATSUMOTO, Ryotaro
dc.contributor.authorTANAKA, Yu
dc.contributor.authorKIKUTA, Kazuhiro
dc.contributor.authorKATAOKA, Fumiya
dc.contributor.authorSASAKI, Akira
dc.contributor.authorLE RHUN, Marc
dc.contributor.authorAUDIN, Hela
dc.contributor.authorLACHAUX, Alain
dc.contributor.authorCAUMONT, Bernard
dc.contributor.authorLORENZO, Diane
dc.contributor.authorBILLIEMAZ, Kareen
dc.contributor.authorBESNARD, Raphael
dc.contributor.authorKOCH, Stephane
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorLAMIREAU, Thierry
dc.contributor.authorDE KONINCK, Xavier
dc.contributor.authorGROUP, Grepan Study
dc.contributor.authorGENIN, Emmanuelle
dc.contributor.authorCOOPER, David N.
dc.contributor.authorMORI, Yasuo
dc.contributor.authorMASAMUNE, Atsushi
dc.contributor.authorFEREC, Claude
dc.date.accessioned2022-01-19T15:35:17Z
dc.date.available2022-01-19T15:35:17Z
dc.date.issued2021-12-19
dc.identifier.issn1059-7794en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/124440
dc.description.abstractEnThe recent discovery of TRPV6 as a pancreatitis susceptibility gene served to identify a novel mechanism of chronic pancreatitis (CP) due to Ca(2+) dysregulation. Herein, we analyzed TRPV6 in 81 probands with hereditary CP (HCP), 204 probands with familial CP (FCP) and 462 patients with idiopathic CP (ICP) by targeted next-generation sequencing. We identified 25 rare nonsynonymous TRPV6 variants, 18 of which had not been previously reported. All 18 variants were characterized by a Ca(2+) imaging assay, with 8 being identified as functionally deficient. Evaluation of functionally deficient variants in the three CP cohorts revealed two novel findings: (i) functionally deficient TRPV6 variants appear to occur more frequently in HCP/FCP patients than in ICP patients (3.2% vs. 1.5%) and (ii) functionally deficient TRPV6 variants found in HCP and FCP probands appear to be more frequently co-inherited with known risk variants in SPINK1, CTRC and/or CFTR than those found in ICP patients (66.7% vs 28.6%). Additionally, genetic analysis of available HCP and FCP family members revealed complex patterns of inheritance in some families. Our findings confirm that functionally deficient TRPV6 variants represent an important contributor to CP. Importantly, functionally deficient TRPV6 variants account for a significant proportion of cases of HCP/FCP. This article is protected by copyright. All rights reserved.
dc.language.isoENen_US
dc.subject.enChronic pancreatitis
dc.subject.enComplex disease
dc.subject.enGenetic variant
dc.subject.enGenotype-phenotype relationship
dc.subject.enTargeted next-generation sequencing
dc.subject.enTRPV6 gene
dc.title.enFunctionally deficient TRPV6 variants contribute to hereditary and familial chronic pancreatitis
dc.typeArticle de revueen_US
dc.identifier.doi10.1002/humu.24315en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed34923708en_US
bordeaux.journalHuman Mutationen_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamLEHA_BPH
bordeaux.teamLEHA_BPH
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03535241
hal.version1
hal.date.transferred2022-01-19T15:35:21Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Human%20Mutation&rft.date=2021-12-19&rft.eissn=1059-7794&rft.issn=1059-7794&rft.au=HAMADA,%20Shin&MASSON,%20Emmanuelle&CHEN,%20Jian%20Min&SAKAGUCHI,%20Reiko&REBOURS,%20Vinciane&rft.genre=article


Fichier(s) constituant ce document

FichiersTailleFormatVue

Il n'y a pas de fichiers associés à ce document.

Ce document figure dans la(les) collection(s) suivante(s)

Afficher la notice abrégée