title: Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity-onset diabetes of the young (MODY). Mutations in brief no. 162. Online.
abstract: The maturity-onset diabetes of the young (MODY), an autosomal dominant form of non-insulin dependent diabetes mellitus (NIDDM), is caused by mutations in the glucokinase (GK, MODY 2) and in the hepatocyte nuclear factor 1a (MODY 3) and 4a (MODY 1) genes. We have screened the glucokinase gene by the polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) in fifteen subjects with clinical characteristics of MODY and one parent with NIDDM, impaired glucose tolerance or gestational diabetes.  PCR products with abnormal mobility in DGGE were directly sequenced. We have identified four mutant alleles, three of them (G80S, E221K, G227C) are new missense mutations located in or near the region of the active site cleft of the enzyme. The mutations co-segregate with hyperglycemia in the families of the three probands, whose biochemical and clinical phenotype is similar to other individuals with MODY 2 mutations.
authors.affiliation: Molecular Endocrinology Unit, Department of Internal Medicine and Endocrinology Unit, Department of Pediatrics, University of Milan, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Guazzini
authors.forename: D
authors.initials: D
authors.lastname: Gaffi
authors.forename: D
authors.initials: D
authors.lastname: Mainieri
authors.forename: G
authors.initials: G
authors.lastname: Multari
authors.forename: R
authors.initials: R
authors.lastname: Cordera
authors.forename: S
authors.initials: S
authors.lastname: Bertolini
authors.forename: G
authors.initials: G
authors.lastname: Pozza
authors.forename: F
authors.initials: F
authors.lastname: Meschi
authors.forename: F
authors.initials: F
authors.lastname: Barbetti
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D007558:Italy; D020125:Mutation, Missense / Q000235:genetics*
chemical_list: D005941:Glucokinase