Mantovani Vilma, Salardi Silvana, Cerreta Vincenzo, Bastia Daniela, Cenci Marinella, Ragni Luca, Zucchini Stefano, Parente Raffaele, Cicognani Alessandro
Laboratorio Centralizzato Settore Genetica, Policlinico S.Orsola-Malpighi, Bologna, Italy.
Hum Mutat. 2003 Oct;22(4):338. doi: 10.1002/humu.9179.
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.
青年发病的成年型糖尿病（MODY）是一组临床异质性疾病，其特征为早发性非胰岛素依赖型糖尿病、常染色体显性遗传以及胰腺β细胞功能的原发性缺陷。葡萄糖激酶（GCK）基因突变占MODY的8%-56%，在南欧的患病率最高。在对28个意大利裔MODY家族进行GCK基因突变筛查时，我们鉴定出17种不同的突变（患病率为61%），其中包括8种先前未描述的突变。新的序列变异包括5种错义突变（外显子4中的p.Lys161Asn c.483G>C、外显子5中的p.Phe171Leu c.511T>C以及外显子7中的p.Thr228Ala c.682A>G、p.Thr228Arg c.683C>G、p.Gly258Cys c.772G>T）；一种无义突变（外显子9中的p.Ser383Ter c.1148C>A）；内含子9中的剪接位点变异c.1253+1G>T；以及外显子10中12个核苷酸的缺失（p.Ser433_Ile436del c.1298_1309del12）。我们的研究表明，GCK/MODY2基因突变是意大利人群中MODY的常见病因，拓宽了我们对自然发生的GCK突变谱的认识。
