Identification of eight novel glucokinase mutations in Italian children with maturity-onset diabetes of the young.

Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of disorders characterized by early onset non-insulin-dependent diabetes mellitus, autosomal dominant inheritance, and primary defect in the function of the beta cells of the pancreas. Mutations in the glucokinase (GCK) gene account for 8%-56% of MODY, with the highest prevalences being found in the southern Europe. While screening for GCK mutations in 28 MODY families of Italian origin, we identified 17 different mutations (corresponding to 61% prevalence), including eight previously undescribed ones. The novel sequence variants included five missense mutations (p.Lys161Asn c.483G>C in exon 4, p.Phe171Leu c.511T>C in exon 5 and p.Thr228Ala c.682A>G, p.Thr228Arg c.683C>G, p.Gly258Cys c.772G>T in exon 7), one nonsense mutation (p.Ser383Ter c.1148C>A in exon 9), the splice site variant c.1253+1G>T in intron 9, and the deletion of 12 nucleotides in exon 10 (p.Ser433_Ile436del c.1298_1309del12). Our study indicates that mutations in the GCK/MODY2 gene are a very common cause of MODY in the Italian population and broadens our knowledge of the naturally occurring GCK mutation repertoire.

Mantovani V ，Salardi S ，Cerreta V ，Bastia D ，Cenci M ，Ragni L ，Zucchini S ，Parente R ，Cicognani A ... -  《-》

Identification of novel GCK and HNF1A/TCF1 mutations and polymorphisms in German families with maturity-onset diabetes of the young (MODY).

Toaima D ，Näke A ，Wendenburg J ，Praedicow K ，Rohayem J ，Engel K ，Galler A ，Gahr M ，Lee-Kirsch MA ... -  《-》

Diagnostic screening of MODY2/GCK mutations in the Norwegian MODY Registry.

Sagen JV ，Bjørkhaug L ，Molnes J ，Raeder H ，Grevle L ，Søvik O ，Molven A ，Njølstad PR ... -  《-》

Glucokinase gene mutation screening in Argentinean clinically characterized MODY patients.

Mutations in the glucokinase gene (GCK) produce a subtype of Maturity onset diabetes in the young (MODY), named MODY 2. To date over than 190 different mutations have been identified, distributed over the coding regions and the exon-intron boundaries of the gene. The aim of this work was to study the nature and frequency of mutations in the GCK gene, in a MODY clinically characterized Argentinean population. Seventy unrelated individuals were selected based on MODY clinical features. The study methodology consisted in PCR amplification of the coding regions of the GCK gene, SSCP electrophoresis analysis of the amplified fragments and direct sequencing of the fragments with abnormal electrophoresis pattern. We identified a total of six patients with mutations in the GCK gene. This included two novel mutations: g.1831C>A, g.3792T>A, one already reported by our group, g.168fsdelC (same mutation in two non-related patients) and two already reported: p.Gln138Pro and p.Gly261Glu. With that data, we could establish the prevalence of MODY 2 among the patients in study reaching to 8.6%. The main contribution of this study is to inform about two novel mutations not described to date and to make an approach to the establishment of the prevalence of MODY 2 in the population under study. These findings contribute to confirm the allelic heterogeneity of GCK gene mutations and may provide an insight into the structure-function relationship of the GCK.

Lopez AP ，Foscaldi SA ，Pérez MS ，Krochik G ，Rodríguez M ，Traversa M ，Puchulu FM ，Hirschler V ，Bergada I ，Frechtel GD ... -  《-》

GCK and HNF1A mutations in Canadian families with maturity onset diabetes of the young (MODY).

Maturity onset diabetes of the young (MODY) is a genetically heterogeneous form of type 2 diabetes that is characterized by autosomal dominant inheritance, onset in early adulthood and a primary defect in insulin secretion. Mutations in at least six genes have been shown to underlie MODY, including mutations in GCK (encoding glucokinase, also called MODY2) and mutations in HNF1A (encoding hepatocyte nuclear factor-1alpha, also called MODY3). We sequenced genomic DNA from probands of seven Canadian MODY families. In four probands, we detected four novel GCK mutations, namely IVS2-7G>A, G72R, T206R and S263P. In three other probands, we detected three HNF1A mutations, of which two were novel, namely 1051delCA and Q250X, and one had been previously reported, namely R131Q. The novel mutations expand the spectrum of MODY mutations. In addition, knowledge of the specific defect can be used to pre-symptomatically identify family members at risk for developing MODY.

Cao H ，Shorey S ，Robinson J ，Metzger DL ，Stewart L ，Cummings E ，Hegele RA ... -  《-》