Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes.
We describe a codon 299 mutation in the glucokinase gene in a British pedigree with maturity-onset diabetes of the young (MODY) resulting in a substitution of glycine to arginine. One out of fifty patients diagnosed with classical late-onset type 2 diabetes mellitus was also found to have this mutation. All nine relatives of this patient who have inherited the mutation have type 2 diabetes, although six others without the mutation are also present with diabetes. The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes.
Stoffel
M
M
Howard Hughes Medical Institute, University of Chicago, Illinois 60637.
Patel
P
P
Lo
Y M
YM
Hattersley
A T
AT
Lucassen
A M
AM
Page
R
R
Bell
J I
JI
Bell
G I
GI
Turner
R C
RC
Wainscoat
J S
JS
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000235:genetics*; D005091:Exons; D005260:Female; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation
D004247:DNA; D005941:Glucokinase