胰岛素基因突变致永久性新生儿糖尿病一例及文献复习  

Permanent neonatal diabetes mellitus caused by a mutation in insulin gene:a case report and literature review

作　　者：付俊玲[1] 王彤[1] 邓明群 翟笑 肖新华[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院内分泌科卫生部内分泌重点实验室,100730

出　　处：《中华糖尿病杂志》2019年第11期730-735,共6页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：国家重点研发计划(2017YFC1309603,2016YFA0101002);国家自然科学基金(81170736,81570715,81870579);中国医学科学院医学表观遗传中心(2017PT31036,2018PT31021)。

摘　　要：目的探讨胰岛素基因突变致新生儿糖尿病(NDM)的临床和遗传学特点。方法对北京协和医院2017年12月诊断的一例永久性NDM(PNDM)患者的临床特征、实验室资料进行分析;运用Sanger测序技术对先证者及其父母进行ATP敏感钾通道编码基因(KCNJ11、ABCC8)和胰岛素基因测序。总结既往报道的胰岛素基因突变致NDM病例的临床资料,分析其临床特点。结果先证者检测到胰岛素基因(NM_000207.2)第2号外显子c.265C>T(p.R89C)杂合突变,该突变导致胰岛素结构发生改变而致病(PNDM)o通过文献复习和病例对比发现迄今已有12种不同的胰岛素基因外显子区域突变致NDM,均表现为PNDM胰岛素基因突变致PNDM发病年龄差别较大.从几周至几岁不等,常以糖尿病酮症酸中毒或血糖水平显著升高为主要特征,C肽水平极低,需依赖胰岛素治疗。结论中国人群存在胰岛素基因R89C突变导致的PNDM;临床上可疑PNDM患者应早期进行KCNJI1和ABCC8和胰岛素基因检测。Objective To explore the clinical and genetic characteristics of neonatal diabetes mellitus(NDM)induced by insulin gene mutation.Methods A Chinese pedigree of permanent neonatal diabetes mellitus(PNDM)diagnosed in Peking Union Medical College Hospital in December 2017 was analyzed for the clinical characteristics and laboratory examinations.Sanger sequencing was performed to identify mutations in KCNJ 11.ABCC8 and insulin gene in proband and her parents.Data of NDM induced by mutations in insulin gene were collected and analyzed.Results A heterozygous mutation in insulin gene(NM_000207.2)located in exon 2(c.265C>T;p.R89C)was identified in the proband.The mutation changes the structure of insulin molecule.Literature review found that there were altogether 12 pathogenic mutations in insulin gene which had been reported to result in NDM.All NDM caused by mutations in insulin gene were classified as PNDM.The onset age of PNDM with mutations in the insulin gene ranges widely,from several weeks to several years,usually with diabetic ketoacidosis or marked hyperglycemia,with very low or undetectable C-peptide values.The patients usually need to be treated with insulin once diagnosed.Conclusion There are PNDM pedigrees caused by insulin gene(R89C)heterozygous mutation in Chinese population.Genetic testing including channel genes(KCNJ 11 and ABCC8)and insulin gene should be conducted in patients with suspected PNDM for early diagnosis and appropriate treatment.

关 键 词：糖尿病 婴儿 新生 胰岛素基因 基因突变 胰岛素治疗 

分 类 号：R58[医药卫生—内分泌]