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dc.contributor.authorJellas, Khadija el
dc.contributor.authorDušátková, Petra
dc.contributor.authorHaldorsen, Ingfrid S.
dc.contributor.authorMolnes, Janne
dc.contributor.authorTjora, Erling
dc.contributor.authorJohansson, Bente Berg
dc.contributor.authorFjeld, Karianne
dc.contributor.authorJohansson, Stefan
dc.contributor.authorPrůhová, Štěpánka
dc.contributor.authorGroop, Leif
dc.contributor.authorLöhr, J. Matthias
dc.contributor.authorNjølstad, Pål Rasmus
dc.contributor.authorMolven, Anders
dc.description.abstractContext Maturity onset diabetes of the young, type 8 (MODY8) is associated with mutations in the CEL gene, which encodes the digestive enzyme carboxyl ester lipase. Several diabetes cases and families have in recent years been attributed to mutations in CEL without any functional or clinical evidence provided. Objective To facilitate correct MODY8 diagnostics, we screened 2 cohorts of diabetes patients and delineated the phenotype. Methods Young, lean Swedish and Finnish patients with a diagnosis of type 2 diabetes (352 cases, 406 controls) were screened for mutations in the CEL gene. We also screened 58 Czech MODY cases who had tested negative for common MODY genes. For CEL mutation-positive subjects, family history was recorded, and clinical investigations and pancreatic imaging performed. Results Two cases (1 Swedish and 1 Czech) with germline mutation in CEL were identified. Clinical and radiological investigations of these 2 probands and their families revealed dominantly inherited insulin-dependent diabetes, pancreatic exocrine dysfunction, and atrophic pancreas with lipomatosis and cysts. Notably, hereditary pancreatitis was the predominant phenotype in 1 pedigree. Both families carried single-base pair deletions in the proximal part of the CEL variable number of tandem repeat (VNTR) region in exon 11. The mutations are predicted to lead to aberrant protein tails that make the CEL protein susceptible to aggregation. Conclusion The diagnosis of MODY8 requires a pancreatic exocrine phenotype and a deletion in the CEL VNTR in addition to dominantly inherited diabetes. CEL screening may be warranted also in families with hereditary pancreatitis of unknown genetic etiology.en_US
dc.publisherOxford University Pressen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleTwo New Mutations in the CEL Gene Causing Diabetes and Hereditary Pancreatitis: How to Correctly Identify MODY8 Casesen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright The Author(s) 2021en_US
dc.source.journalJournal of Clinical Endocrinology and Metabolism (JCEM)en_US
dc.identifier.citationJournal of Clinical Endocrinology and Metabolism. 2022, 107 (4), e1455-e1466.en_US

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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Med mindre annet er angitt, så er denne innførselen lisensiert som Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal