LABSIEM (Laboratory for the Study of Inborn Errors of Metabolism), Pediatric Clinic, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, 16100 Genoa, Italy.
Int J Mol Sci. 2023 Feb 17;24(4):4034. doi: 10.3390/ijms24044034.
Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes mellitus (DM) that accounts for around 2-5% of all types of diabetes. Autosomal dominant inheritance in pathogenic variations of 14 genes related to β-cell functions can lead to monogenic types of diabetes. In Italy, GCK/MODY is the most frequent form and it is caused by mutations of the glucokinase (GCK). Patients with GCK/MODY usually have stable mild fasting hyperglycaemia with mildly elevated HbA1c levels and rarely need pharmacological treatment. Molecular analysis of the GCK coding exons was carried out by Sanger sequencing in eight Italian patients. All the probands were found to be heterozygous carriers of a pathogenic gross insertion/deletion c.1279_1358delinsTTACA; p.Ser426_Ala454delinsLeuGln. It was previously described for the first time by our group in a large cohort of Italian GCK/MODY patients. The higher levels of HbA1c (6.57% vs. 6.1%), and the higher percentage of patients requiring insulin therapy (25% vs. 2%) compared to the previously studied Italian patients with GCK/MODY, suggest that the mutation discovered could be responsible for a clinically worse form of GCK/MODY. Moreover, as all the patients carrying this variant share an origin from the same geographic area (Liguria), we postulate a possible founder effect and we propose to name it the "pesto" mutation.
青少年发病的成年型糖尿病（MODY）是一种单基因形式的糖尿病，占所有类型糖尿病的 2-5%左右。与β细胞功能相关的 14 个基因的致病性变异中的常染色体显性遗传可导致单基因类型的糖尿病。在意大利，GCK/MODY 是最常见的形式，它是由葡萄糖激酶（GCK）的突变引起的。GCK/MODY 患者通常有稳定的轻度空腹高血糖，HbA1c 水平轻度升高，很少需要药物治疗。对 8 名意大利患者的 GCK 编码外显子进行了 Sanger 测序的分子分析。所有先证者均被发现为致病性大片段插入/缺失 c.1279_1358delinsTTACA；p.Ser426_Ala454delinsLeuGln 的杂合子携带者。该突变先前由我们的研究小组在一大群意大利 GCK/MODY 患者中首次描述。与之前研究过的意大利 GCK/MODY 患者相比，HbA1c 水平更高（6.57%对 6.1%），需要胰岛素治疗的患者比例更高（25%对 2%），这表明发现的突变可能导致 GCK/MODY 更严重的临床表现。此外，由于所有携带这种变异的患者都来自同一地理区域（利古里亚），我们推测可能存在一个共同的起源，我们将其命名为“香蒜酱”突变。
