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首页> 外文期刊>Pediatric diabetes. >Glyburide ameliorates motor coordination and glucose homeostasis in a child with diabetes associated with the KCNJ11/S225T, del226-232 mutation
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Glyburide ameliorates motor coordination and glucose homeostasis in a child with diabetes associated with the KCNJ11/S225T, del226-232 mutation

机译：格列本脲改善了与KCNJ11 / S225T，del226-232突变相关的糖尿病患儿的运动协调和葡萄糖稳态

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Gain-of-function mutations of KCNJ11 can cause permanent neonatal diabetes mellitus, but only rarely after 6?months of age. Specific uncommon mutations KCNJ11give rise to a syndrome defined as developmental delay, epilepsy, and neonatal diabetes (DEND), or more frequently to a milder sub-type lacking epilepsy, denoted as intermediate-DEND (iDEND). Our aim was to consider a possible monogenic etiology in a 12-yr-old boy with early onset diabetes and mild neurological features. We studied a subject diagnosed with diabetes at 21?months of age, and negative to type 1 diabetes autoantibodies testing. He had learning difficulties during primary school, and a single episode of seizures at the age of 10 yr. We performed direct DNA sequencing of the KCNJ11 gene with subsequent functional study of mutated channels in COSm6 cells. The patient's clinical response to oral glyburide (Glyb) was assessed. Motor coordination was evaluated before and after 6 and 12?months of Glyb therapy. Sequencing of the KCNJ11 gene detected the novel, spontaneous mutation S225T, combined with deletion of amino acids 226232. In vitro studies revealed that the mutation results in a KATP channel with reduced sensitivity to the inhibitory action of ATP. Glyb improved diabetes control (hemoglobin A1c on insulin: 52?mmol/mol/6.9%; on Glyb: 36?mmol/mol/5.4%) and also performance on motor coordination tests that were impaired before the switch of therapy. We conclude that KCNJ11/S225T, del226-232 mutation caused a mild iDEND form in our patient. KCNJ11 should be considered as the etiology of diabetes even beyond the neonatal period if present in combination with negative autoantibody testing and even mild neurological symptoms.
机译：KCNJ11的功能获得性突变可引起永久性新生儿糖尿病，但在6个月大以后很少发生。特定的罕见突变KCNJ11导致发展为发育迟缓，癫痫和新生儿糖尿病（DEND）的综合征，或更常见的是缺乏癫痫的轻度亚型，称为中度DEND（iDEND）。我们的目的是考虑在12岁的男孩中出现早期糖尿病和轻度神经功能的单基因病因。我们研究了一个被诊断患有21岁以下糖尿病且1型糖尿病自身抗体检测阴性的受试者。他上小学时有学习困难，并且在10岁时发作过一次癫痫发作。我们对KCNJ11基因进行了直接DNA测序，随后对COSm6细胞中突变通道进行了功能研究。评估患者对口服格列本脲（Glyb）的临床反应。在Glyb治疗6和12个月之前和之后评估运动协调性。 KCNJ11基因的测序检测到新的，自发的突变S225T，加上氨基酸226232的缺失。体外研究表明，该突变导致KATP通道对ATP抑制作用的敏感性降低。 Glyb改善了糖尿病控制（胰岛素上的血红蛋白A1c：52？mmol / mol / 6.9％; Glyb：36？mmol / mol / 5.4％），并且在治疗切换前受损的运动协调能力也得到改善。我们得出的结论是，KCNJ11 / S225T，del226-232突变在我们的患者中引起了轻度的iDEND形式。如果将KCNJ11与阴性自身抗体检测甚至轻微的神经系统症状相结合，即使在新生儿期后也应被视为糖尿病的病因。

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