Analysis of mutations in the glucokinase gene in people clinically characterized as MODY2 without a family history of diabetes.
BACKGROUND
Maturity-onset diabetes of the young 2 (MODY2) is a form of diabetes that is clinically characterized by early age at onset and mild hyperglycemia, and has a low risk of late complications. It is often underdiagnosed due to its mild symptoms. To date, over 600 different GCK/MODY2 mutations have been reported. Despite only a few de novo mutations having been described, recent studies have reported the detection of a higher frequency of this kind of mutation. Therefore, de novo mutations could be more frequent than previously described. Even though common recommendations regarding the diagnosis of monogenic diabetes include the existence of a strong family history of diabetes, here we describe the study of mutations in two families with a symptomatic individual with clear clinical features of MODY2 but without any family history of diabetes.


METHODS
Genetic diagnosis in a group of participants with MODY2 characteristics was carried out by direct sequencing of coding regions of the GCK gene and analysis of mutations found using bioinformatics tools.


RESULTS
We found two de novo mutations, one of them novel, constituting 14.29% of all the participants who were phenotyped as MODY2.


CONCLUSIONS
The number of mutations in GCK/MODY2 or even other MODY-related genes is undoubtedly underestimated, as accepted criteria for performing genetic tests include family history of the pathology. These cases illustrate the value of analyzing the GCK gene in patients with clinical features of MODY2, even in the absence of family history of the condition as it is essential for establishing the correct treatment.
Genetics Division, 4to piso sala 5, Hospital de Clinicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires CP 1120, Argentina. Electronic address: aplopez@ffyb.uba.ar.
Ariel Pablo
AP
Lopez
Genetics Division, 4to piso sala 5, Hospital de Clinicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires CP 1120, Argentina. Electronic address: alejandrodedios@hotmail.com.
Alejandro
A
de Dios
Manlab Laboratory, M. T. de Alvear 2263, Buenos Aires CP 1122, Argentina. Electronic address: ignacio.chiesa@manlab.com.ar.
Ignacio
I
Chiesa
Manlab Laboratory, M. T. de Alvear 2263, Buenos Aires CP 1122, Argentina. Electronic address: maria.perez@manlab.com.ar.
Maria Silvia
MS
Perez
Genetics Division, 4to piso sala 5, Hospital de Clinicas "José de San Martín", Universidad de Buenos Aires, Buenos Aires CP 1120, Argentina. Electronic address: gfrechtel@ffyb.uba.ar.
Gustavo Daniel
GD
Frechtel
D000293:Adolescent; D001118:Argentina / Q000453:epidemiology; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005941:Glucokinase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence; D012189:Retrospective Studies
D004247:DNA; D005941:Glucokinase
De novo mutation; Diabetes; GCK gene; MODY2