title: Haploinsufficiency at GCK gene is not a frequent event in MODY2 patients.
abstract: 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.
authors.affiliation: Endocrinology and Diabetes Research Group, Hospital de Cruces, Barakaldo, Basque Country, Spain.
authors.forename: Intza
authors.initials: I
authors.lastname: Garin
authors.forename: Itxaso
authors.initials: I
authors.lastname: Rica
authors.forename: Itziar
authors.initials: I
authors.lastname: Estalella
authors.forename: Mirentxu
authors.initials: M
authors.lastname: Oyarzabal
authors.forename: Mercedes
authors.initials: M
authors.lastname: Rodríguez-Rigual
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: San Pedro
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pérez-Nanclares
authors.forename: Eduardo
authors.initials: E
authors.lastname: Fernández-Rebollo
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Busturia
authors.forename: Luis
authors.initials: L
authors.lastname: Castaño
authors.forename: Guiomar
authors.initials: G
authors.lastname: Pérez de Nanclares
mesh_terms: 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
chemical_list: D000081410:Germinal Center Kinases; D017346:Protein Serine-Threonine Kinases