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. PATIENTS AND 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. CONCLUSION: 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.
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. PATIENTS AND 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. CONCLUSION: 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: Camilla B Jensen; Esther Zimmermann; Michael Gamborg; Berit L Heitmann; Jennifer L Baker; Allan Vaag; Thorkild I A Sørensen Journal: Diabetologia Date: 2015-06-16 Impact factor: 10.122
Authors: Gabriella de Medeiros Abreu; Roberta Magalhães Tarantino; Ana Carolina Proença da Fonseca; Juliana Rosa Ferreira de Oliveira Andrade; Ritiele Bastos de Souza; Camila de Almeida Pereira Dias Soares; Amanda Cambraia; Pedro Hernan Cabello; Melanie Rodacki; Lenita Zajdenverg; Verônica Marques Zembrzuski; Mário Campos Junior Journal: Front Endocrinol (Lausanne) Date: 2022-05-03 Impact factor: 6.055
Authors: Lucas S de Santana; Lilian A Caetano; Aline D Costa-Riquetto; Pedro C Franco; Renata P Dotto; André F Reis; Letícia S Weinert; Sandra P Silveiro; Marcio F Vendramini; Flaviene A do Prado; Giovanna C P Abrahão; Ana Gregória F P de Almeida; Maria da G Rodrigues Tavares; Wagner Rodrigo B Gonçalves; Augusto C Santomauro Junior; Bruno Halpern; Alexander A L Jorge; Marcia Nery; Milena G Teles Journal: Mol Genet Genomic Med Date: 2019-10-08 Impact factor: 2.183