Paediatrics Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy.
Clin Genet. 2013 Jan;83(1):83-7. doi: 10.1111/j.1399-0004.2012.01856.x. Epub 2012 Mar 26.
Mutations in the glucokinase (GCK) gene are the most frequent cause of maturity onset diabetes of the young (MODY) in Italy. We evaluated GCK mutations in 32 unrelated patients younger than 18 years who had been diagnosed with MODY. Eleven different GCK heterozygous mutations were identified in 22 (68.7%) of the 32 probands. Nine mutations were missense and two were nonsense. Three of these mutations (E17X, P59S and E372X) have not been described previously and were shown to be associated with hyperglycaemia. Several prediction methods suggested that the E17X and E372X mutations result in a premature truncated protein and that the P59S mutation is pathogenic. This idea was further supported by evidence suggesting that Proline 59 is a highly conserved amino acid residue and that the P59S mutation does not appear to be present in non-diabetic controls and in sequence variant databases. Furthermore, this mutation was found in six (27.3%) of the patients from the same geographical area, Gargano, pointing to the existence of a founder effect, which was confirmed by microsatellite analysis.
葡萄糖激酶（GCK）基因突变是意大利青年人成年发病型糖尿病（MODY）最常见的病因。我们评估了 32 名年龄小于 18 岁且被诊断为 MODY 的非相关患者的 GCK 突变。在 32 名先证者中的 22 名（68.7%）发现了 11 种不同的 GCK 杂合突变。9 种突变是错义突变，2 种是无义突变。其中 3 种突变（E17X、P59S 和 E372X）以前没有描述过，与高血糖有关。几种预测方法表明，E17X 和 E372X 突变导致提前产生截短蛋白，而 P59S 突变是致病性的。脯氨酸 59 是高度保守的氨基酸残基的证据进一步支持了这一观点，而且 P59S 突变似乎不存在于非糖尿病对照和序列变异数据库中。此外，这种突变在来自同一地理区域（加尔加诺）的 6 名（27.3%）患者中被发现，这表明存在一个创始效应，微卫星分析证实了这一点。
