title: Single-strand conformation polymorphism analysis of the glucose transporter gene GLUT1 in maturity-onset diabetes of the young.
abstract: Maturity-onset diabetes of the young (MODY), an autosomal dominant, early-onset form of type-2 diabetes, is caused by mutations in five different genes all leading to defect(s) in the pancreatic beta cell. However, some patients with this form of diabetes do not bear a mutation in any of the known (MODY1-MODY5) loci, a notion prompting the search for new MODY genes. Clinical and genetic data point toward a defect in beta cell function in the majority of patients with MODY, and partners of the glucose-sensing device are reasonable functional candidates. The high-capacity glucose transporter GLUT2 has the ideal kinetic features for performing this task. However, complete GLUT2 deficiency in humans leads to hepato-renal glycogenosis (Fanconi-Bickel syndrome), and heterozygous GLUT2 mutations apparently behave in a recessive manner. Furthermore, in the human beta cell GLUT1 mRNA is predominant when compared to GLUT2 and glucose influx appears to be largely mediated by this low-Km transporter. Thus, we looked for the presence of sequence variants by polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) within the GLUT1 gene in 90 Italian pedigrees negative at the search for mutations in glucokinase (MODY2) and hepatocyte nuclear factor-1alpha (MODY3), the two genes responsible for about 60% of MODY cases in Italian children. We found three already described silent mutations and a new single base deletion in position -173 of the 5' regulatory region. The -173de1A variant, which was detected in the heterozygous or homozygous state in 30.8% of MODY patients examined and is located in a Nuclear Factor Y binding sequence, is not associated with hyperglycemia in affected relatives of MODY probands. In conclusion, it appears from these results that the glucose transporter gene GLUT1 is unlikely to play a major role in the etiology of MODY diabetes.
authors.affiliation: Department of Clinical Science, University of Rome La Sapienza, Italy. baroni@caspur.it
authors.forename: M G
authors.initials: MG
authors.lastname: Baroni
authors.forename: F
authors.initials: F
authors.lastname: Sentinelli
authors.forename: O
authors.initials: O
authors.lastname: Massa
authors.forename: S
authors.initials: S
authors.lastname: Romeo
authors.forename: C
authors.initials: C
authors.lastname: Colombo
authors.forename: U
authors.initials: U
authors.lastname: Di Mario
authors.forename: F
authors.initials: F
authors.lastname: Barbetti
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016384:Consensus Sequence / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons / Q000235:genetics; D051272:Glucose Transporter Type 1; D006801:Humans; D007558:Italy; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D020218:Response Elements / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D023081:CCAAT-Binding Factor; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D014157:Transcription Factors; C402244:nuclear factor Y