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

作　　者：王彤[1] 李明敏[1] 于淼[1] 卢超霞[2] 张化冰[1] 平凡[1] 张茜[1] 齐翠娟[1] 郑佳[1] 王晓晶[1] 付俊玲[1] 肖新华[1] Wang Tong;Li Mingmin;Yu Miao;Lu Chaoxia;Zhang Huabing;Ping Fan;Zhang Qian;Qi Cuijuan;Zheng Jia;Wang Xiaojing;Fu Junling;Xiao Xinhua(Department of Endocrinology,Key Laboratory of Endocrinology,Ministry of Health,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences ＆ Peking Union Medical College,Beijing 100730,China)

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 [2]中国医学科学院基础医学研究所北京协和医学院基础学院医学分子生物学国家重点实验室麦库西克-张孝骞协和遗传医学中心

出　　处：《中华糖尿病杂志》2018年第9期596-600,共5页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：国家自然科学基金（81570715）;国家重点研发计划（2017YFC1309603）;北京市科委单基因糖尿病鉴别路径研究（D141107005314002）;卫生部.诺和诺德糖尿病研究英才基金（RT201501）;2015年度公益性行业科研专项（201502011）

摘　　要：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一临床表型关系。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FOXP3p．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。相同致病基冈型、不同临床表型背后的分子机制尚有待进一步研究。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 canying 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. Tile underlying molecular mechanism remains to be further studied.

关 键 词：糖尿病 婴儿 新生 叉头状转录因子P3 IPEX综合征 

分 类 号：R587.1[医药卫生—内分泌]