2例新生儿糖尿病患者致病基因型及疗效分析  

Genetic analysis of two cases with neonatal diabetes mellitus and the research on therapy

作　　者：刘颖[1] 宋福英[1] 叶雪[1] 陈晓波[1] 

机构地区：[1]首都儿科研究所附属儿童医院,北京100020

出　　处：《中国医刊》2015年第8期63-67,共5页Chinese Journal of Medicine

摘　　要：目的分析2例新生儿糖尿病患者的致病基因型及探讨格列苯脲的疗效。方法选取2013年4月至2014年10月本院收治并确诊的新生儿糖尿病患儿2例,对其进行常见致病基因KCNJ11、ABCC8、INS和GCK 4个基因测序分析,并复习相关文献,根据基因结果给予硫脲类药物试验性治疗。结果病例1的KCNJ11基因检测到3个杂合突变,其中Arg201His为已报道的永久性新生儿糖尿病致病突变,余2个位点为无致病性的单核苷酸多态性,ABCC8、INS和GCK基因检测未发现突变;病例2的KCNJ11基因检测到2个杂合突变,位点与病例1非致病性突变位点相同,余基因测序未发现异常。给予病例1格列苯脲口服疗效满意,胰岛素减停后随访血糖平稳;给予病例2格列苯脲试验性用药,疗效不佳。结论新生儿糖尿病的遗传发病机制复杂,KCNJ11基因突变可导致新生儿糖尿病的发生,格列苯脲适于用治疗KCNJ11基因突变阳性病例。Objective To sequence gene mutations in 2 probands with neonatal diabetes mellitus （ NDM） and ob-serve the treatment of glibenclamide on two cases. Method 2 NDM cases hospitalized in Children’ s Hospital Affili-ated to Capital Institute of Pediatrics during April 2013 to October 2014 were studied. KCNJ11, ABCC8, INS and GCK genes were sequenced in one family and a proband. And according to the literature and outcomes, glib-enclamide were given for oral therapy. Result Three heterozygous mutations of KCNJ11 gene were detected in case 1, among which, Arg201His mutation had been proved to be causative for permanent NDM. The other two mutations were reported single nucleotide polymorphisms （ SNP） without pathogenicity. No mutation was detected in the rest three genes. Two heterozygous mutations of KCNJ11 gene were found in case 2. The mutation cites were produced SNP with no pathogenic. Drug of glibenclamide did significant effectiveness upon case 1. Follow-up for oral taken without insulin was satisfied. While in case 2, glibenclamide seemed to be invalid. Conclusion The genetic patho-genesis for NDM was complicated. KCNJ11 gene mutation might result in the onset of NDM. Oral taken of glib-enclamide was suitable for KCNJ11 gene mutation case instead of insulin.

关 键 词：新生儿糖尿病 KCNJ11基因 三磷酸腺苷敏感性钾通道 格列苯脲 

分 类 号：R725.8[医药卫生—儿科]