Six novel mutations in the <i>GCK</i> gene in MODY patients

Pintérová, Daniela; Ek, Jakob; Kološtová, Katarína; Průhová, Štěpánka; Novota, P; Romzova, Marianna; Feigerlová, Eva; Černá, Marie; Lebl, Jan; Pedersen, Oluf; Hansen, Torben

doi:10.1111/j.1399-0004.2006.00729.x

Cited by 11 publications

(11 citation statements)

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“…We detected 46 different mutations summarized in Table 2. Twenty‐two of them were detected by dHPLC and characterized by sequencing and described in our previous studies (6, 10). Thirteen mutations are novel, previously unpublished: p.Gly81Asp, p.Asp124Asn, p.Asn180fs, p.Thr209Lys, p.Val226Glu, p.Val244fs, p.Val277Arg, p.Gly385Trp, p.Val412fs, p.Glu442stop, IVS2+1G>A, IVS5+1G>T, and IVS7–1G>C. Some mutations were detected in more than one apparently unrelated family: p.Glu40Lys (in 20 families), p.Gly318Arg (12 families), p.Leu315His (seven families), p.Val33Ala (six families), p.Cys220X (five families), p.Cys434Tyr (four families), p.Glu268stop (three families), and seven mutations found in two families each.…”

Section: Resultsmentioning

confidence: 94%

“…Sixty‐six probands had been tested in previously published studies (6, 10) using the dHPLC as a screening method. Twenty probands with clinical suspicion on GCK‐MODY were dHPLC negative.…”

Section: Methodsmentioning

confidence: 99%

“…Nowadays, direct sequencing of all samples prevails. In our previous studies (6, 10), the dHPLC was used as a screening method for the investigation of GCK .…”

mentioning

confidence: 99%

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Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations

et al. 2010

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The study shows a relatively high proportion of GCK mutations among individuals with GCK-like phenotype, confirming the effectiveness of carefully applied clinical criteria prior to genetic testing. In the Czech MODY registry, GCK-MODY represents the biggest subgroup of MODY (35%). We report several prevalent GCK mutations with a likely founder effect in the Czech population. Furthermore, our results provide ground for a possible recommendation to reinspect all negative results previously obtained by screening using dHPLC.

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Section: Resultsmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

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Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations

et al. 2010

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“…Thus far, about 200 GCK mutations have been reported and its frequency is higher in European Caucasians, particularly in those from France and Italy [6]. The identification of a GCK mutation in subjects whose clinical phenotype is suggestive of MODY usually distinguishes patients with a benign prognosis (GCK MODY) from those with a severe hyperglycemia (HNF1A MODY and other MODY forms) because the diagnosis cannot be always made on clinical grounds alone.…”

Section: Introductionmentioning

confidence: 99%

Glucokinase Gene Mutations: Structural and Genotype-Phenotype Analyses in MODY Children from South Italy

et al. 2008

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BackgroundMaturity onset diabetes of the young type 2 (or GCK MODY) is a genetic form of diabetes mellitus provoked by mutations in the glucokinase gene (GCK).Methodology/Principal FindingsWe screened the GCK gene by direct sequencing in 30 patients from South Italy with suspected MODY. The mutation-induced structural alterations in the protein were analyzed by molecular modeling. The patients' biochemical, clinical and anamnestic data were obtained. Mutations were detected in 16/30 patients (53%); 9 of the 12 mutations identified were novel (p.Glu70Asp, p.Phe123Leu, p.Asp132Asn, p.His137Asp, p.Gly162Asp, p.Thr168Ala, p.Arg392Ser, p.Glu290X, p.Gln106_Met107delinsLeu) and are in regions involved in structural rearrangements required for catalysis. The prevalence of mutation sites was higher in the small domain (7/12: ∼59%) than in the large (4/12: 33%) domain or in the connection (1/12: 8%) region of the protein. Mild diabetic phenotypes were detected in almost all patients [mean (SD) OGTT = 7.8 mMol/L (1.8)] and mean triglyceride levels were lower in mutated than in unmutated GCK patients (p = 0.04).ConclusionsThe prevalence of GCK MODY is high in southern Italy, and the GCK small domain is a hot spot for MODY mutations. Both the severity of the GCK mutation and the genetic background seem to play a relevant role in the GCK MODY phenotype. Indeed, a partial genotype-phenotype correlation was identified in related patients (3 pairs of siblings) but not in two unrelated children bearing the same mutation. Thus, the molecular approach allows the physician to confirm the diagnosis and to predict severity of the mutation.

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“…The GCK MOdY form is caused by mutations in the GCK gene. Thus far, about 200 GCK mutations have been reported and their frequency is higher in European Caucasians, particularly in those from France and Italy (Pinterova et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Screening of mutations in the GCK gene in Jordanian maturity-onset diabetes of the young type 2 (MODY2) patients

Khalil¹,

F²,

Khamaiseh³

et al. 2009

Genet. Mol. Res.

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ABSTRACT. Maturity-onset diabetes of the young type 2 (MOdY2) is a genetic form of diabetes mellitus caused by mutations in the glucokinase gene (GCK). We assessed the frequency of GCK gene mutations in Jordanian suspected MOdY2 patients. We screened exons 7, 8 and 9, which are specific for pancreatic glucokinase, for mutations at positions 682A>G, p.T228A; 895G>C, p.G299R, and 1148C>A, p.S383X, respectively, in 250 subjects (100 patients suspected to have MOdY2 and 150 healthy controls without family history of diabetes mellitus). We did not find any association of these mutations in Jordanian suspected MOdY2 patients or in healthy controls, different from data on Caucasian Italian patients screened for the same mutations.

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Six novel mutations in the GCK gene in MODY patients

Cited by 11 publications

References 11 publications

Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations

Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations

Glucokinase Gene Mutations: Structural and Genotype-Phenotype Analyses in MODY Children from South Italy

Screening of mutations in the GCK gene in Jordanian maturity-onset diabetes of the young type 2 (MODY2) patients

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