Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/503
Título : Opposite clinical phenotypes of glucokinase disease: Description of a novel activating mutation and contiguous inactivating mutations in human glucokinase (GCK) gene.
Autor : Barbetti, Fabrizio
Cobo-Vuilleumier, Nadia
Dionisi-Vici, Carlo
Toni, Sonia
Ciampalini, Paolo
Massa, Ornella
Rodriguez-Bada, Pablo
Colombo, Carlo
Lenzi, Lorenzo
Garcia-Gimeno, María A
Bermudez-Silva, Francisco J
Rodriguez de Fonseca, Fernando
Banin, Patrizia
Aledo, Juan C
Baixeras, Elena
Sanz, Pascual
Cuesta-Muñoz, Antonio L
Filiación: [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, Spain.
Palabras clave : Femenino
Predisposición Genética a la Enfermedad
Humanos
Hipoglucemia
Glucoquinasa
Recién Nacido
Cinética
Masculino
Modelos Teóricos
Mutagénesis Sitio-Dirigida
Mutación
Linaje
Fenotipo
MeSH: Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to Disease
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Glucokinase
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hypoglycemia
Medical Subject Headings::Named Groups::Persons::Age Groups::Infant::Infant, Newborn
Medical Subject Headings::Phenomena and Processes::Physical Phenomena::Mechanical Phenomena::Kinetics
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genetic Engineering::Protein Engineering::Mutagenesis, Site-Directed
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Pedigree
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype
Medical Subject Headings::Check Tags::Female
Fecha de publicación : Dec-2009
Editorial : The Endocrine Society
Cita Bibliográfica: Barbetti 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):1983-9
Abstract: Glucokinase 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 reported.
Descripción : Journal Article; Research Support, Non-U.S. Gov't;
URI: http://hdl.handle.net/10668/503
Versión del editor : http://mend.endojournals.org/content/23/12/1983.abstract
DOI: 10.1210/me.2009-0094
ISSN : 0888-8809 (Print)
1944-9917 (Online)
Appears in Collections:01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga
01- Artículos - Hospital Regional de Málaga

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