胰岛素基因新变异所致永久性新生儿糖尿病患儿1例的临床及遗传学分析  

Clinical and genetic analysis of an infant with permanent neonatal diabetes mellitus due to a novel variant of insulin gene

作　　者：李玛丽 李佳[1] 邱世超 宋娜 汪治华[1] Li Mali;Li Jia;Qiu Shichao;Song Na;Wang Zhihua(Department of Endocrinology,Genetics and Metabolism,Xi′an Children′s Hospital,Xi′an,Shaanxi 710003,China)

机构地区：[1]西安市儿童医院内分泌遗传代谢科,西安710003

出　　处：《中华医学遗传学杂志》2023年第1期66-70,共5页Chinese Journal of Medical Genetics

基　　金：西安市科技计划(21YXYJ0013)。

摘　　要：目的分析1例永久性新生儿糖尿病(PNDM)患儿的临床及遗传学特征。方法选取2019年8月于西安市儿童医院就诊的1例PNDM患儿为研究对象。收集患儿的临床资料及实验室检查结果,应用靶向捕获高通量测序进行变异位点分析,针对筛选出的候选靶基因用Sanger测序进行家系验证。结果患儿系4个月26天女婴,以酮症酸中毒起病,空腹血糖24.4 mmol/L,尿糖阳性,血清C肽降低,糖化血红蛋白9.58%,糖尿病自身抗体阴性。基因检测发现患儿胰岛素INS基因存在c.314T>G(p.L105R)杂合变异。Sanger测序证实患儿父母均未携带上述变异,为新发变异。该变异尚未见文献及数据库报道,根据美国医学遗传学与基因组学学会指南,评级为疑似致病变异。结论INS基因c.314T>G(p.L105R)变异可能是该患儿的遗传学病因。对于临床疑似PNDM的患儿建议早期行基因检测。Objective To explore the genetic basis for an infant with permanent neonatal diabetes mellitus(PNDM).Methods Clinical data of the child was collected.Targeted capture-next generation sequencing was carried out to identify the potential variants.Candidate variant was verified by Sanger sequencing of her family members.Results The child was a 4-month-and-26-day female featuring onset of ketoacidosis accompanied with fasting blood glucose of 24.4 mmol/L,positive urine glucose,decreased serum C-peptide,HbA1c of 9.58%,and negative diabetes autoantibody.Genetic testing revealed that she has carried a heterozygous c.314T>G(p.L105R)variant of the INS gene.Sanger sequencing verified that neither of her parents has carried the same variant,which was also unreported in the literature.The variant was classified as likely pathogenic based on the ACMG guidelines.Conclusion The c.314T>G(P.L105R)variant of the INS gene probably underlay the genetic etiology in this child.Genetic testing should be conducted for children with suspected PNDM for early diagnosis and appropriate treatment.

关 键 词：永久性新生儿糖尿病 INS基因 酮症酸中毒 基因变异 

分 类 号：R722.1[医药卫生—儿科]