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 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 GLUT] gene in 90 Italian pedigrees negative at the search for mutations in glucokinase (MODY2) and hepatocyte nuclear factor-1 alpha (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 -173delA 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 GLUT] is unlikely to play a major role in the etiology of MODY diabetes.

Single strand conformation polymorphisms analysis of the glucose transporter gene GLUT1 in maturity-onset diabetes of the young / Baroni, Marco Giorgio; Sentinelli, F; Massa, O; Romeo, S; Colombo, C; Dimario, U; Barbetti, F.. - In: JOURNAL OF MOLECULAR MEDICINE. - ISSN 0946-2716. - 79(June)::(2001), pp. 270-274. [10.1007/s001090100220]

Single strand conformation polymorphisms analysis of the glucose transporter gene GLUT1 in maturity-onset diabetes of the young

BARONI, Marco Giorgio;SENTINELLI F;
2001

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 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 GLUT] gene in 90 Italian pedigrees negative at the search for mutations in glucokinase (MODY2) and hepatocyte nuclear factor-1 alpha (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 -173delA 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 GLUT] is unlikely to play a major role in the etiology of MODY diabetes.
2001
01 Pubblicazione su rivista::01a Articolo in rivista
Single strand conformation polymorphisms analysis of the glucose transporter gene GLUT1 in maturity-onset diabetes of the young / Baroni, Marco Giorgio; Sentinelli, F; Massa, O; Romeo, S; Colombo, C; Dimario, U; Barbetti, F.. - In: JOURNAL OF MOLECULAR MEDICINE. - ISSN 0946-2716. - 79(June)::(2001), pp. 270-274. [10.1007/s001090100220]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/514977
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