Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorBarbetti, Fabrizio-
dc.contributor.authorCobo-Vuilleumier, Nadia-
dc.contributor.authorDionisi-Vici, Carlo-
dc.contributor.authorToni, Sonia-
dc.contributor.authorCiampalini, Paolo-
dc.contributor.authorMassa, Ornella-
dc.contributor.authorRodriguez-Bada, Pablo-
dc.contributor.authorColombo, Carlo-
dc.contributor.authorLenzi, Lorenzo-
dc.contributor.authorGarcia-Gimeno, María A-
dc.contributor.authorBermudez-Silva, Francisco J-
dc.contributor.authorRodriguez de Fonseca, Fernando-
dc.contributor.authorBanin, Patrizia-
dc.contributor.authorAledo, Juan C-
dc.contributor.authorBaixeras, Elena-
dc.contributor.authorSanz, Pascual-
dc.contributor.authorCuesta-Muñoz, Antonio L-
dc.identifier.citationBarbetti F, Cobo-Vuilleumier N, Dionisi-Vici C, Toni S, Ciampalini P, Massa O, et al. Opposite clinical phenotypes of glucokinase disease: Description of a novel activating mutation and contiguous inactivating mutations in human glucokinase (GCK) gene. Mol. Endocrinol.. 2009 Dec; 23(12):1983-9es
dc.identifier.issn0888-8809 (Print)-
dc.identifier.issn1944-9917 (Online)-
dc.descriptionJournal Article; Research Support, Non-U.S. Gov't;es
dc.description.abstractGlucokinase is essential for glucose-stimulated insulin release from the pancreatic beta-cell, serving as glucose sensor in humans. Inactivating or activating mutations of glucokinase lead to different forms of glucokinase disease, i.e. GCK-monogenic diabetes of youth, permanent neonatal diabetes (inactivating mutations), and congenital hyperinsulinism, respectively. Here we present a novel glucokinase gene (GCK)-activating mutation (p.E442K) found in an infant with neonatal hypoglycemia (1.5 mmol/liter) and in two other family members suffering from recurrent hypoglycemic episodes in their childhood and adult life. In contrast to the severe clinical presentation in the index case, functional studies showed only a slight activation of the protein (relative activity index of 3.3). We also report on functional studies of two inactivating mutations of the GCK (p.E440G and p.S441W), contiguous to the activating one, that lead to monogenic diabetes of youth. Interestingly, adult family members carrying the GCK pE440G mutation show an unusually heterogeneous and progressive diabetic phenotype, a feature not typical of GCK-monogenic diabetes of youth. In summary, we identified a novel activating GCK mutation that although being associated with severe neonatal hypoglycemia is characterized by the mildest activation of the glucokinase enzyme of all previously
dc.description.sponsorshipThis work was supported by grants (to A.L.C.-M. and N.C.-V.) from Ministerio de Ciencia e Innovación, Dirección General de Investigación Científica y Técnica (SAF2005-08014; SAF2006-12863) and Junta de Andalucía (SAS/PI-024/2007; SAS/PI-0236/2009).es
dc.publisherThe Endocrine Societyes
dc.relation.ispartofMolecular endocrinology (Baltimore, Md.)es
dc.subjectPredisposición Genética a la Enfermedades
dc.subjectRecién Nacidoes
dc.subjectModelos Teóricoses
dc.subjectMutagénesis Sitio-Dirigidaes
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Diseasees
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Glucokinasees
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humanses
dc.subject.meshMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hypoglycemiaes
dc.subject.meshMedical Subject Headings::Named Groups::Persons::Age Groups::Infant::Infant, Newbornes
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Physical Phenomena::Mechanical Phenomena::Kineticses
dc.subject.meshMedical Subject Headings::Check Tags::Malees
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoreticales
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Engineering::Protein Engineering::Mutagenesis, Site-Directedes
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutationes
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Pedigreees
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotypees
dc.subject.meshMedical Subject Headings::Check Tags::Femalees
dc.titleOpposite clinical phenotypes of glucokinase disease: Description of a novel activating mutation and contiguous inactivating mutations in human glucokinase (GCK)
dc.rights.accessRightsAcceso abiertoes
dc.contributor.authoraffiliation[Barbetti,F; Dionisi-Vici,C; Ciampalini,P; Massa,O; Colombo,C] Bambino Gesú Pediatric Hospital Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy. [Barbetti,F] Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy. Laboratory of Molecular Endocrinology and Metabolism, S Raffaele Biomedical Park Foundation, Rome, Italy. [Cobo-Vuilleumier,N; Rodriguez-Bada,P; Bermudez-Silva,FJ; Rodriguez de Fonseca,F; Aledo,JC; Baixeras,E; Cuesta-Muñoz,AL] Center for the Study of Pancreatic-Cell Diseases. Instituto Mediterráneo para el Avance de la Biotecnología y la Investigación Sanitaria Foundation and Carlos Haya Hospital, Málaga, Spain. [Toni,S; Lenzi,L] Regional Center for Juvenile Diabetes, Meyer Pediatric Hospital, Florence, Italy. [Garcia-Gimeno,MA; Sanz,P] Institute of Biomedicine of Valencia (CSIC). CIBERER-ISCIII, Valencia, Spain. [Banin,P] Pediatric and Adolescent Unit, S. Anna Hospital, Ferrara, Italy. [Aledo,JC] Molecular Biology and Biochemistry Department University of Málaga,
Appears in Collections:01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga
01- Artículos - Hospital Regional de Málaga

Files in This Item:
File Description SizeFormat 
Barbetti_OppositeClinicalPhenotypes.pdfArtículo publicado311,99 kBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons