title: Identification of eight novel glucokinase mutations in Italian children with maturity-onset diabetes of the young.
abstract: Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of disorders characterized by early onset non-insulin-dependent diabetes mellitus, autosomal dominant inheritance, and primary defect in the function of the beta cells of the pancreas. Mutations in the glucokinase (GCK) gene account for 8%-56% of MODY, with the highest prevalences being found in the southern Europe. While screening for GCK mutations in 28 MODY families of Italian origin, we identified 17 different mutations (corresponding to 61% prevalence), including eight previously undescribed ones. The novel sequence variants included five missense mutations (p.Lys161Asn c.483G>C in exon 4, p.Phe171Leu c.511T>C in exon 5 and p.Thr228Ala c.682A>G, p.Thr228Arg c.683C>G, p.Gly258Cys c.772G>T in exon 7), one nonsense mutation (p.Ser383Ter c.1148C>A in exon 9), the splice site variant c.1253+1G>T in intron 9, and the deletion of 12 nucleotides in exon 10 (p.Ser433_Ile436del c.1298_1309del12). Our study indicates that mutations in the GCK/MODY2 gene are a very common cause of MODY in the Italian population and broadens our knowledge of the naturally occurring GCK mutation repertoire.
authors.affiliation: Laboratorio Centralizzato Settore Genetica, Policlinico S.Orsola-Malpighi, Bologna, Italy. mantovan@med.unibo.it
authors.forename: Vilma
authors.initials: V
authors.lastname: Mantovani
authors.forename: Silvana
authors.initials: S
authors.lastname: Salardi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerreta
authors.forename: Daniela
authors.initials: D
authors.lastname: Bastia
authors.forename: Marinella
authors.initials: M
authors.lastname: Cenci
authors.forename: Luca
authors.initials: L
authors.lastname: Ragni
authors.forename: Stefano
authors.initials: S
authors.lastname: Zucchini
authors.forename: Raffaele
authors.initials: R
authors.lastname: Parente
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cicognani
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics*; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010641:Phenotype
chemical_list: D005941:Glucokinase