摘要目的 明确永久性新生儿糖尿病患者的分子遗传学诊断,并评价个体化治疗的效果.方法 对北京协和医院2007年8月至2012年8月收治的1岁内起病的10例永久性新生儿糖尿病患者,用聚合酶链反应(PCR)直接测序法对编码胰岛β细胞ATP敏感性钾通道(KATP)的Kir6.2亚单位和SUR1亚单位的KCNJ11和ABCC8基因进行检测,以明确分子遗传学诊断；对于由编码KATP通道基因突变导致的永久性新生儿糖尿病患者,由皮下胰岛素注射治疗转换为口服格列苯脲治疗并观察疗效.结果 10例永久性新生儿糖尿病患儿中,发现KCNJ11突变3例,均为已知基因突变；ABCC8突变4例,2例为已知基因突变,另外2例的突变位点尚无文献报道.对于已明确是由编码KATP通道基因突变致病的7例患儿,由皮下胰岛素注射治疗转换为口服格列苯脲治疗；共4例转换成功,包括3例KCNJ11突变和1例ABCC8突变患儿,格列苯脲的平均剂量为0.18 mg·kg-1·d-1,成功者接受治疗转换时的病程相对较短(2.0～3.6年).治疗转换成功的患者血糖控制均良好,且未出现低血糖等副作用.结论 编码胰岛β细胞KATP通道的Kir6.2亚单位和SUR1亚单位的KCNJ11和ABCC8基因突变是我国永久性新生儿糖尿病患者常见致病原因,口服磺脲类药物的个体化治疗方案在此类患者中常具有较好疗效和安全性.

abstractsObjective To establish the molecular genetics diagnosis of permanent neonatal diabetes (PNDM) and test personalized medicine.Methods A total of 10 PNDM cases with the onset before 1 year of age and admitted to Peking Union Medical College Hospital from August,2007 to August,2012 were enrolled in this study.Polymerase chain reaction (PCR) product direct sequencing was performed in the 10 cases for mutations in the KCNJ11 and ABCC8 gene.In the PNDM cases identified with mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel(KATP),the patients were switched from insulin injection to oral glibenclamide and were followed up for efficacy and safety.Results Mutations causing KATP-PNDM were identified in seven cases,including 3 in KCNJ11 and 4 in ABCC8.Those KATP-PNDM cases were switched from insulin injection to oral glibenclamide treatment with the mean dosage of 0.18 mg · kg-1 · d-1 and 4 cases succeeded (3 KCNJ11 and 1 ABCC8).The successfully switched cases manifested relatively short disease duration at the time of switch with a range of 2.0 to 3.6 years and all showed good glycemic control with no adverse events including hypoglycemia.Conclusions Mutations in the genes encoding the two subunits of the ATP-sensitive potassium channel are common in the Chinese PNDM.Oral sulfonylurea therapy,personalized medicine for KATP-PNDM,leads to good efficacy and safety profiles in most of them.