TY - JOUR
T1 - Early-onset Type II diabetes mellitus in Italian families due to mutations in the genes encoding hepatic nuclear factor 1α and glucokinase
AU - Gragnoli, C.
AU - Cockburn, B. N.
AU - Chiaramonte, F.
AU - Gorini, A.
AU - Marietti, G.
AU - Marozzi, G.
AU - Signorini, A. M.
N1 - Funding Information:
HNF-1a/n = 54 chromosome; T513T is in the control group; GCK/n = 40 chromosomes; HNF-4a/n = 32 chromosomes aNew polymorphism Acknowledgements. We are grateful to the Santo Spirito Hospital nursing staff for blood collection and to G. Bell for his great academic support. We thank J. Habener for helpful editorial suggestions in the preparation of the manuscript. These studies were supported by the Howard Hughes Medical Institute, NIH grants DK-20 595 and -44840, and an unrestricted grant from Bristol-Meyers Squibb. A Juvenile Diabetes Foundation International Fellowship supported C. Gragnoli. We are thankful to M. P. Patrizi, G. Peruzzi and N. Piumelli of BIOS Center, Rome for DNA preparation.
PY - 2001
Y1 - 2001
N2 - Aims/hypothesis. Maturity-onset-diabetes of the young (MODY) is caused by mutations in at least five different genes. Our aim was to determine the prevalence of the most common MODY genes in Italian families with early-onset Type II (non-insulin-dependent) diabetes mellitus. Methods. We screened 28 Italian early-onset Type II diabetic families (diagnosis < 35 years) for mutations in the hepatic nuclear factor-4α, (MODY1), glucokinase (MODY2) and hepatic nuclear factor-1α (MODY3). Both strands of exons, flanking introns and minimal promoter regions of the above-mentioned genes were amplified using polymerase chain reaction and were sequenced directly. Results. We identified four different mutations, three of which are not described, (W113X, G42P43fsCC → A, H514R) and four new polymorphisms (G184G, T513T, IVS3-nt47delG, IVS1- nt53C → G) in the hepatic nuclear factor-1α gene, two new potential mutations (G44S, IVS4nt + 7C → T) and three new polymorphisms (promoter-nt84C → G, IVS9 + nt8C → T, IVS9 + nt49G → A) in the glucokinase gene, and a new polymorphism (IVS1c-nt11T → G) in the hepatic nuclear factor-4α gene. Conclusion/interpretation. Mutations in the hepatic nuclear factor-1α and glucokinase are associated with Type II diabetes in 14% and 7% of Italian families, respectively. Our findings provide an impetus for screening Italian MODY and early-non Type II diabetic families for mutations in the above mentioned genes to identify relatives at risk who could benefit from primary prevention care.
AB - Aims/hypothesis. Maturity-onset-diabetes of the young (MODY) is caused by mutations in at least five different genes. Our aim was to determine the prevalence of the most common MODY genes in Italian families with early-onset Type II (non-insulin-dependent) diabetes mellitus. Methods. We screened 28 Italian early-onset Type II diabetic families (diagnosis < 35 years) for mutations in the hepatic nuclear factor-4α, (MODY1), glucokinase (MODY2) and hepatic nuclear factor-1α (MODY3). Both strands of exons, flanking introns and minimal promoter regions of the above-mentioned genes were amplified using polymerase chain reaction and were sequenced directly. Results. We identified four different mutations, three of which are not described, (W113X, G42P43fsCC → A, H514R) and four new polymorphisms (G184G, T513T, IVS3-nt47delG, IVS1- nt53C → G) in the hepatic nuclear factor-1α gene, two new potential mutations (G44S, IVS4nt + 7C → T) and three new polymorphisms (promoter-nt84C → G, IVS9 + nt8C → T, IVS9 + nt49G → A) in the glucokinase gene, and a new polymorphism (IVS1c-nt11T → G) in the hepatic nuclear factor-4α gene. Conclusion/interpretation. Mutations in the hepatic nuclear factor-1α and glucokinase are associated with Type II diabetes in 14% and 7% of Italian families, respectively. Our findings provide an impetus for screening Italian MODY and early-non Type II diabetic families for mutations in the above mentioned genes to identify relatives at risk who could benefit from primary prevention care.
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U2 - 10.1007/s001250100644
DO - 10.1007/s001250100644
M3 - Article
C2 - 11692182
AN - SCOPUS:0034771385
VL - 44
SP - 1326
EP - 1329
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 10
ER -