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dc.contributor.authorAbdulkarim, B.en
dc.contributor.authorNicolino, M.en
dc.contributor.authorIgoillo-Esteve, M.en
dc.contributor.authorDaures, M.en
dc.contributor.authorRomero, S.en
dc.contributor.authorPhilippi, A.en
dc.contributor.authorSenée, V.en
dc.contributor.authorLopes, M.en
dc.contributor.authorCunha, D. A.en
dc.contributor.authorHarding, H. P.en
dc.contributor.authorDerbois, C.en
dc.contributor.authorBendelac, N.en
dc.contributor.authorHattersley, Andrew T.en
dc.contributor.authorEizirik, D. L.en
dc.contributor.authorRon, D.en
dc.contributor.authorCnop, M.en
dc.contributor.authorJulier, C.en
dc.identifier.citationA Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly. 2015, 64 (11):3951-62 Diabetesen
dc.description.abstractDysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic β-cell failure and diabetes. Here, we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2α phosphorylation [CReP]) encoding the regulatory subunit of an eIF2α-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly. The R658C mutation in PPP1R15B affects a conserved amino acid within the domain important for protein phosphatase 1 (PP1) binding. The R658C mutation decreases PP1 binding and eIF2α dephosphorylation and results in β-cell apoptosis. Our findings support the concept that dysregulated eIF2α phosphorylation, whether decreased by mutation of the kinase (EIF2AK3) in Wolcott-Rallison syndrome or increased by mutation of the phosphatase (PPP1R15B), is deleterious to β-cells and other secretory tissues, resulting in diabetes associated with multisystem abnormalities.en
dc.publisherAmerican Diabetes Associationen
dc.rightsArchived with thanks to Diabetesen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Endocrinology::Diabetesen
dc.titleA Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly.en
dc.typeJournal Articleen
dc.typeCase Reporten
dc.typeResearch Support, Non-U.S. Gov'ten
dc.description.noteThis article is freely available via the publisher's site - click on the 'Additional Link' above to access the full text.en
dc.description.funding084812/Wellcome Trust/United Kingdom 084812/Z/08/Z/Wellcome Trust/United Kingdom 098395/Wellcome Trust/United Kingdom 100140/Wellcome Trust/United Kingdomen

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