Female, 21 years old, with no children.
At 17 years of age, DM was diagnosed due to polydipsia and polyuria, associated with fasting glucose 130 mg/dl, confirmed with postprandial oral glucose tolerance test (OGTT) of 75 g: 234 mg/dl.
DM1 was ruled out by negative autoantibodies and normal C-peptide, HbA1c 6.8% at admission and urine without glycosuria.
On physical examination, no signs of IR, height 1.56 m and weight 44.5 kg, BMI 18 kg/m2 were found.
Non-pharmacological treatment was indicated and metformin 850 mg/2 times a day.
He remained HbA1c between 6-7% for 4 years without complications.
In January 2015 metformin was suspended due to gastric intolerance and considering the evolution and family history of DM, it was suggested that MODY could present.
DM was studied in relatives with PTGO, searching for DM in the father.
His brother had abnormal blood glucose.
The mother had no DM.
* Normal range: 1.1 - 4.4 ng/ml.
The family history highlights a strong presence of DM along the paternal line, where 8 of 9 siblings of the father of the index case are diagnosed with DM2, in addition to both grandparents.
Only grandmother and aunt have DM2.
The application of the University of Exeter5 was used, estimating that the patient has MODY with a probability of 75.5%.
It was decided to carry out a family genetic study, for which the informed consent of the participants and the approval of the Ethics Committee of Hospital San Juan de Dios were available.
A genetic-molecular analysis was performed (Labortion of genetics in the Red-Christus Santiago, Chile) of exons 1 to 10 of the GCK gene by direct sequencing of coding regions.
The patient had a mutation in position 1343 in exon 10 of GCK gene, corresponding to a change of guanine to adenine (1343 G>A); in the other heterozygous allele this mutation was not found (patient).
The father and brother have the same mutation of the GCK gene heterozygously.
The mother showed both wild alleles, so it is neither MODY2 nor has DM.
The variant found is probably pathogenic because it generates a non-synonymous or missense change of the amino acid (aa) glycine by aspartic acid (Gly448Asp)GC in the glycokinase enzyme.
These results allow to establish the presence of MODY2 in a Chilean family due to a mutation not previously described.
