RT Journal Article
T1 Opposite clinical phenotypes of glucokinase disease: Description of a novel activating mutation and contiguous inactivating mutations in human glucokinase (GCK) gene.
A1 Barbetti, Fabrizio
A1 Cobo-Vuilleumier, Nadia
A1 Dionisi-Vici, Carlo
A1 Toni, Sonia
A1 Ciampalini, Paolo
A1 Massa, Ornella
A1 Rodriguez-Bada, Pablo
A1 Colombo, Carlo
A1 Lenzi, Lorenzo
A1 Garcia-Gimeno, María A
A1 Bermudez-Silva, Francisco J
A1 Rodriguez de Fonseca, Fernando
A1 Banin, Patrizia
A1 Aledo, Juan C
A1 Baixeras, Elena
A1 Sanz, Pascual
A1 Cuesta-Muñoz, Antonio L
K1 Femenino
K1 Predisposición Genética a la Enfermedad
K1 Humanos
K1 Hipoglucemia
K1 Glucoquinasa
K1 Recién Nacido
K1 Cinética
K1 Masculino
K1 Modelos Teóricos
K1 Mutagénesis Sitio-Dirigida
K1 Mutación
K1 Linaje
K1 Fenotipo
AB 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.
PB The Endocrine Society
SN 0888-8809
YR 2009
FD 2009-12
LK http://hdl.handle.net/10668/503
UL http://hdl.handle.net/10668/503
LA en
NO 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
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 8, 2025