摘要目的 通过对1例青少年的成人起病型糖尿病(MODY)6型患者的临床特征及分子遗传学资料总结,阐释该病的临床特点及分子遗传机制.方法 本研究收集了临床上1例可疑MODY患者的临床资料及辅助检查结果,对该患者进行外周血DNA提取,进行特殊类型糖尿病检测包的二代测序后进行Sanger一代测序验证,将基因检测结果与遗传学数据库比对,遗传学软件进行功能预测及蛋白质结构预测.此外,通过检索文献回顾了国内外已报道的MODY6的临床特点.结果 本研究发现了一个导致MODY6的新的神经分化因子1(NEUROD1)基因突变(p.R103L),该基因突变位点位于NEUROD1中的碱性螺旋-袢-螺旋结构域(bHLH),该结构域为NEUROD1与DNA进行结合的部位,其突变影响了NEUROD1对胰岛素基因的调节.回顾文献,我们发现NEUROD1基因杂合突变外显不完全,发病年龄以及临床异质性强.此外,妊娠期可能是诊断MODY6的重要窗口.既往文献报道的两个中国人NEUROD1突变的家系中,NEUROD1基因突变被认为是2型糖尿病的致病基因.而本研究发现的这例NEUROD1突变患者符合典型的MODY特点:起病年龄＜25岁,无胰岛素抵抗及自身免疫证据,家族中有连续三代糖尿病家族史.结论 本研究发现了新的NEUROD1基因突变并阐述了其可能的致病机制,这也是中国人群中首例符合典型MODY特点的MODY6病例.

abstractsObjective To describe the clinical characteristics of a patient with maturity-onset diabetes of the young (MODY) type 6 (MODY6) and explore the molecular genetic mechanism.Methods The clinical data of a clinically suspected MODY patient was collected.The peripheral blood DNA was extracted from the patient.After next generation sequencing,Sanger sequencing was performed to verify the genetic test results.The function of genetic variation was predicted by genetic function software and protein structure was predicted by SWISS-MODLE.With other reported cases,we also reviewed and summarized the clinical feature of MODY6.Results This study found a novel neurogenic differentiation 1 (NEUROD1)mutation (p.R103L) of MODY6,which was located in the DNA binding area,a basic helix-loop-helix domain,resulting in dysfunctional regulation of the insulin gene.Heterozygous NEUROD1 mutation had an incomplete penetrance of the phenotype,with a strong clinical heterogeneity.In addition,pregnancy might be an important time window for diagnosing MODY6.The NEUROD1 gene mutation was considered being a susceptible gene of type 2 diabetes in the previous reported Chinese family of NEUROD1 mutation.However,we reported the first Chinese case of MODY6 that met the typical MODY characteristics:diabetes on set before the age of 25,no evidence of insulin resistance and autoimmunity and three successive generations of diabetes in his family.Conclusions A novel NEUROD1 gene mutation is identified and its possible pathogenic mechanism is described.It is the first case of MODY6 in Chinese population that meets the typical MODY characteristics.