叉头状转录因子P3基因突变致新生儿糖尿病三例分子遗传学及临床特征分析
Genetic and clinical features of 3 cases of neonatal diabetes mellitus caused by forkhead box P3 gene mutation
目的 研究中国人群中叉头状转录因子P3(FOXP3)基因突变所致新生儿糖尿病(NDM)患者的临床特点以及基因型-临床表型关系.方法 纳入自2007年8月至2016年8月就诊于北京协和医院的可疑NDM患者50例,详细收集临床资料,通过目标区域捕获测序技术对21个已知NDM致病基因进行测序,寻找可疑致病基因,用Sanger测序进行验证,明确分子遗传学诊断.结果 遗传学确诊FOXP3-NDM患者3例,分别携带FOXP3 p.R312H、p.V408M、p.P133L半合子突变.此3例患者均表现为单纯的永久性NDM,随访至9~12岁均未合并IPEX综合征常见的其他相关临床表现,仅需使用胰岛素降糖治疗.而国外已报道的、甚至是携带相同致病突变的FOXP3-NDM病例均表现为除NDM外还合并其他多种自身免疫相关疾病,均需使用免疫抑制治疗.结论 本研究首次报道中国人群中的FOXP3-NDM患者,且表现为与国外已报道病例截然不同的临床表型.相同致病基因型、不同临床表型背后的分子机制尚有待进一步研究.
更多Objective To elucidate the clinical characteristics and genotype-phenotype relationships of Chinese patients with neonatal diabetes mellitus (NDM) caused by forkhead box P3 (FOXP3) gene mutations (FOXP3-NDM).Methods A total of 50 suspected patients with NDM were recruited from Peking Union Medical College Hospital.After the detailed collection of clinical information,target sequencing of 21 known causative genes of NDM were performed for molecular genetic diagnosis.Results Three patients with FOXP3-NDM were identified,separately carrying FOXP3 p.R312H,p.V408M,and p.P133L hemizygous mutations.All these 3 patients showed simple permanent NDM,without other common manifestations of IPEX syndrome until 9-12 years old.And they only need insulin therapy.However,all the foreign reported cases presented multiple autoimmune diseases besides NDM,and needed immunosuppressive therapy,even with the same mutation.Conclusion This is the first report of Chinese FOXP3-NDM patients,which showed totally different clinical phenotypes from foreign reported cases.The underlying molecular mechanism remains to be further studied.
More- 浏览:173
- 被引:0
- 下载:196
相似文献
- 中文期刊
- 外文期刊
- 学位论文
- 会议论文