Haploinsufficiency at GCK gene is not a frequent event in MODY2 patients.
OBJECTIVE
The aim of this study was to characterize glucokinase (GCK) alterations in maturity-onset diabetes of the young 2 (MODY2)-suspected patients and to investigate their clinical characteristics in relation to the parental origin of the mutation.


METHODS
We studied a group of 57 unrelated Spanish patients presenting with MODY2 phenotype. Patients without mutation in the coding region of the GCK gene were screened for rearrangements by Multiplex Ligation-dependent Probe Amplification (MLPA). After classification according to the parental origin of the mutation, clinical characteristics were compared between the groups.


RESULTS
We detected a point mutation or small deletion or insertion of the GCK gene in 47 patients (82.5%); 19 mutations were novel. In addition, we found a whole-gene deletion by MLPA. Patients carrying a GCK gene defect and those with MODY of unknown genetic origin shows similar phenotypes. Comparison of clinical parameters according to the origin of the mutation did not show any differences in the birth weight (BW) nor in age at diagnosis. Patients who inherited the mutation from the father had higher fasting glucose levels at diagnosis.


CONCLUSIONS
Although the presence of haploinsufficiency of GCK is not a common cause of MODY2, gene dose analysis should be performed when no mutation is found. Strict maternal euglycaemia can contribute to intrauterine growth restriction and low BW when the foetus has inherited the GCK mutation from the mother. As foetal genotype in generally is not known, serial foetal abdominal scans may act as a surrogate for this.
Garin
Intza
I
Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, Basque Country, Spain.
Rica
Itxaso
I
Estalella
Itziar
I
Oyarzabal
Mirentxu
M
Rodríguez-Rigual
Mercedes
M
San Pedro
Jose Ignacio
JI
Pérez-Nanclares
Gustavo
G
Fernández-Rebollo
Eduardo
E
Busturia
Maria Angeles
MA
Castaño
Luis
L
Pérez de Nanclares
Guiomar
G
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D020022:Genetic Predisposition to Disease; D000081410:Germinal Center Kinases; D006239:Haplotypes; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D013030:Spain
D000081410:Germinal Center Kinases; D017346:Protein Serine-Threonine Kinases