GCK-MODY (MODY 2) Caused by a Novel p.Phe330Ser Mutation

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Abstract

Maturity onset diabetes of the young (MODY) is a monogenic form of diabetes inherited as an autosomal dominant trait. The second most common cause is GCK-MODY due to heterozygous mutations in the GCK gene which impair the glucokinase function through different mechanisms such as enzymatic activity, protein stability, and increased interaction with its receptor. The enzyme normally acts as a glucose sensor in the pancreatic beta cell and regulates insulin secretion. We report here a three-generation nonobese family diagnosed with diabetes. All affected family members presented with mild hyperglycemia and mostly slightly elevated hemoglobin A1c values. Genetic testing revealed a novel heterozygous T → C exchange in exon 8 of the GCK gene which resulted in a phenylalanine ₃₃₀ TTC → serine (TCC)/p.Phe330Ser/F330S substitution.

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Most cited references 37

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Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young.

Stefan S. Fajans, Graeme I. Bell, Kenneth Polonsky (2001)

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Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.

Sian Ellard, Cécile Saint Cloment, Kevin Colclough … (2009)

Glucokinase is a key regulatory enzyme in the pancreatic beta-cell. It plays a crucial role in the regulation of insulin secretion and has been termed the glucose sensor in pancreatic beta-cells. Given its central role in the regulation of insulin release it is understandable that mutations in the gene encoding glucokinase (GCK) can cause both hyper- and hypoglycemia. Heterozygous inactivating mutations in GCK cause maturity-onset diabetes of the young (MODY) subtype glucokinase (GCK), characterized by mild fasting hyperglycemia, which is present at birth but often only detected later in life during screening for other purposes. Homozygous inactivating GCK mutations result in a more severe phenotype presenting at birth as permanent neonatal diabetes mellitus (PNDM). A growing number of heterozygous activating GCK mutations that cause hypoglycemia have also been reported. A total of 620 mutations in the GCK gene have been described in a total of 1,441 families. There are no common mutations, and the mutations are distributed throughout the gene. The majority of activating mutations cluster in a discrete region of the protein termed the allosteric activator site. The identification of a GCK mutation in patients with both hyper- and hypoglycemia has implications for the clinical course and clinical management of their disorder.

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Familial hyperinsulinism caused by an activating glucokinase mutation.

Miguel Cuesta, Margaret C. Stanley, Betsy Herold … (1998)

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Author and article information

Journal

Journal ID (nlm-ta): ISRN Pediatr

Journal ID (publisher-id): PEDIATRICS

Title: ISRN Pediatrics

Publisher: International Scholarly Research Network

ISSN (Print): 2090-469X

ISSN (Electronic): 2090-4703

Publication date (Print): 2011

Publication date (Electronic): 26 April 2011

Volume: 2011

Electronic Location Identifier: 676549

Affiliations

¹Division of Pediatric Endocrinology, Department of Pediatrics, Technische Universität München Kölner Platz 1, 80804 Munich, Germany

²Institut für Diabetesforschung, Helmholtz Zentrum München, 85764 Neuherberg, Germany

³Department of Clinical Chemistry, Klinikum Großhadern, Ludwig Maximilian University of Munich, 81377 Munich, Germany

Author notes

*Walter Bonfig: walter.bonfig@ 123456lrz.tum.de

Academic Editor: G. Zuccotti

Article

DOI: 10.5402/2011/676549

PMC ID: 3263572

PubMed ID: 22389783

SO-VID: b9aee25b-d2bd-444c-a276-5917aa410b3f

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 27 January 2011

Date accepted : 13 March 2011

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