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.
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2008 |
|---|---|
| Erschienen: |
2008 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:68 |
|---|---|
| Enthalten in: |
Clinical endocrinology - 68(2008), 6 vom: 01. Juni, Seite 873-8 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Garin, Intza [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
EC 2.7.11.1 |
|---|
| Anmerkungen: |
Date Completed 23.07.2009 Date Revised 03.12.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/j.1365-2265.2008.03214.x |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM17736677X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM17736677X | ||
| 003 | DE-627 | ||
| 005 | 20231223150042.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231223s2008 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/j.1365-2265.2008.03214.x |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0591.xml |
| 035 | |a (DE-627)NLM17736677X | ||
| 035 | |a (NLM)18248649 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Garin, Intza |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Haploinsufficiency at GCK gene is not a frequent event in MODY2 patients |
| 264 | 1 | |c 2008 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.07.2009 | ||
| 500 | |a Date Revised 03.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Germinal Center Kinases |2 NLM | |
| 650 | 7 | |a Protein Serine-Threonine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Rica, Itxaso |e verfasserin |4 aut | |
| 700 | 1 | |a Estalella, Itziar |e verfasserin |4 aut | |
| 700 | 1 | |a Oyarzabal, Mirentxu |e verfasserin |4 aut | |
| 700 | 1 | |a Rodríguez-Rigual, Mercedes |e verfasserin |4 aut | |
| 700 | 1 | |a San Pedro, Jose Ignacio |e verfasserin |4 aut | |
| 700 | 1 | |a Pérez-Nanclares, Gustavo |e verfasserin |4 aut | |
| 700 | 1 | |a Fernández-Rebollo, Eduardo |e verfasserin |4 aut | |
| 700 | 1 | |a Busturia, Maria Angeles |e verfasserin |4 aut | |
| 700 | 1 | |a Castaño, Luis |e verfasserin |4 aut | |
| 700 | 1 | |a Pérez de Nanclares, Guiomar |e verfasserin |4 aut | |
| 700 | 0 | |a Spanish MODY Group |e verfasserin |4 aut | |
| 700 | 1 | |a Abellán, M |e investigator |4 oth | |
| 700 | 1 | |a Espiga, J |e investigator |4 oth | |
| 700 | 1 | |a Boronat, M |e investigator |4 oth | |
| 700 | 1 | |a Galicia, I |e investigator |4 oth | |
| 700 | 1 | |a Lamas |e investigator |4 oth | |
| 700 | 1 | |a López-Capapé, M |e investigator |4 oth | |
| 700 | 1 | |a Unanue, G |e investigator |4 oth | |
| 700 | 1 | |a Fernández, C |e investigator |4 oth | |
| 700 | 1 | |a Sobradillo, B |e investigator |4 oth | |
| 700 | 1 | |a Rivas, F |e investigator |4 oth | |
| 700 | 1 | |a Leiva, I |e investigator |4 oth | |
| 700 | 1 | |a Prieto, J |e investigator |4 oth | |
| 700 | 1 | |a López, M J |e investigator |4 oth | |
| 700 | 1 | |a Hermoso, F |e investigator |4 oth | |
| 700 | 1 | |a Bueno, G |e investigator |4 oth | |
| 700 | 1 | |a Tapia, L |e investigator |4 oth | |
| 700 | 1 | |a Cortazar, A |e investigator |4 oth | |
| 700 | 1 | |a Gaztambide, S |e investigator |4 oth | |
| 700 | 1 | |a Martul, P |e investigator |4 oth | |
| 700 | 1 | |a Quintana, B |e investigator |4 oth | |
| 700 | 1 | |a Santamaría, J |e investigator |4 oth | |
| 700 | 1 | |a Vázquez, F |e investigator |4 oth | |
| 700 | 1 | |a Vela, A |e investigator |4 oth | |
| 700 | 1 | |a Aleixandre, F |e investigator |4 oth | |
| 700 | 1 | |a Reig, C |e investigator |4 oth | |
| 700 | 1 | |a Borrás, V |e investigator |4 oth | |
| 700 | 1 | |a Santos, L |e investigator |4 oth | |
| 700 | 1 | |a Calvo, T |e investigator |4 oth | |
| 700 | 1 | |a Rodríguez-Rigual, M |e investigator |4 oth | |
| 700 | 1 | |a Casas, J |e investigator |4 oth | |
| 700 | 1 | |a Gómez Vida, J |e investigator |4 oth | |
| 700 | 1 | |a Forga, L |e investigator |4 oth | |
| 700 | 1 | |a Menéndez, E |e investigator |4 oth | |
| 700 | 1 | |a Rial Rodríguez |e investigator |4 oth | |
| 700 | 1 | |a Luengo, J L |e investigator |4 oth | |
| 700 | 1 | |a Alonso, M |e investigator |4 oth | |
| 700 | 1 | |a Barrio, R |e investigator |4 oth | |
| 700 | 1 | |a Gastaldo, E |e investigator |4 oth | |
| 700 | 1 | |a Blasco, L |e investigator |4 oth | |
| 700 | 1 | |a Robira, A |e investigator |4 oth | |
| 700 | 1 | |a Garcia-Cuartero, B |e investigator |4 oth | |
| 700 | 1 | |a Bel, J |e investigator |4 oth | |
| 700 | 1 | |a Antón, A |e investigator |4 oth | |
| 700 | 1 | |a Diez, I |e investigator |4 oth | |
| 700 | 1 | |a Rodriguez, A |e investigator |4 oth | |
| 700 | 1 | |a Ruiz-Cano, R |e investigator |4 oth | |
| 700 | 1 | |a Jiménez-Bustos, J M |e investigator |4 oth | |
| 700 | 1 | |a Ramirez Fernandez |e investigator |4 oth | |
| 700 | 1 | |a Hernando, C |e investigator |4 oth | |
| 700 | 1 | |a Cedeño, J |e investigator |4 oth | |
| 700 | 1 | |a Barreiro, J |e investigator |4 oth | |
| 700 | 1 | |a Luzuriaga, C |e investigator |4 oth | |
| 700 | 1 | |a Diaz de Greñu, C |e investigator |4 oth | |
| 700 | 1 | |a Espino, R |e investigator |4 oth | |
| 700 | 1 | |a Oyarzabal, M |e investigator |4 oth | |
| 700 | 1 | |a Gómez-Gila, A |e investigator |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical endocrinology |d 1972 |g 68(2008), 6 vom: 01. Juni, Seite 873-8 |w (DE-627)NLM000089117 |x 1365-2265 |7 nnns |
| 773 | 1 | 8 | |g volume:68 |g year:2008 |g number:6 |g day:01 |g month:06 |g pages:873-8 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/j.1365-2265.2008.03214.x |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 68 |j 2008 |e 6 |b 01 |c 06 |h 873-8 | ||