先天性中枢性甲状腺功能减退症1例的临床和基因分析  

Clinical and Gene Variation Analysis of Congenital Central Hypothyroidism:A Case Report

作　　者：周旭晨[1] 郭改丽 吕道祯 石俊辉 张婷[2,3] 洪芳 ZHOU Xu-chen;GUO Gai-li;LV Dao-zhen;SHI Jun-hui;ZHANG Ting;HONG Fang(Department of Neonatal,the First Division Hospital of Xinjiang Production and Construction Corps,Xinjiang Aksu,843000;Department of Genetics and Metabolism,Children’s Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang,310052;National Clinical Research Center for Child Health,Hangzhou,Zhejiang,310052)

机构地区：[1]新疆生产建设兵团第一师医院新生儿科,新疆阿克苏843000 [2]浙江大学医学院附属儿童医院遗传与代谢科,杭州310052 [3]国家儿童健康与疾病临床医学研究中心,杭州310052

出　　处：《农垦医学》2020年第3期281-285,共5页Journal of Nongken Medicine

摘　　要：目的:探讨1例先天性中枢性甲状腺功能减退症的临床、生化及遗传学特点。方法:对患儿的临床表现、甲状腺功能及治疗随访等进行分析,应用二代测序技术进行遗传学检测并对变异位点进行生物信息学软件评估。结果:患儿在新生儿期存在中枢性甲状腺功能减退、黄疸延迟消退、贫血和体格生长落后,不伴其他垂体激素缺乏,左甲状腺素替代治疗2年后体格指标好转,认知、运动功能无异常;包含目的基因的高通量测序显示患儿携带母源性的X连锁IGSF1基因c.1918G>T(p.G661W)半合子错义突变,数据库提示非多态性,生物信息学软件分析该位点变异导致蛋白糖基化不稳定,中度危害。结论:国内首次报道1例X连锁IGSF1突变导致的罕见男性先天性中枢性甲状腺功能减退症,基因检测有助于该病的诊断、治疗及家系的遗传咨询。Objective:To investigate the clinical,biochemical and genetic characteristics of a child of congenital central hypothyroidism.Methods:The clinical manifestations,thyroid function and treatment follow-up were analyzed,the next generation sequencing was performed,and the variant was further analyzed with bioinformatics software.Results:In the neonatal period,the child presented central hypothyroidism,delayed regression of jaundice,anemia and physical growth retardation without other pituitary hormone deficiency.After 2 years of levothyroxine(L-T4)replacement therapy,the physical indicators improved,and the cognitive and motor functions were not abnormal.High-throughput sequencing containing the target gene showed that the child carried maternal X-linked IGSF1 gene c.1918 G>T(p.G661 W)hemizygote missense mutation.The database indicated non-polymorphism,and bioinformatics software analyzed that the mutation at this site resulted in instability and moderate harm to glycosylation.Conclusion:A rare male congenital central hypothyroidism caused by X-linked IGSF1 mutation was reported for the first time in China.Gene detection is helpful for the diagnosis,treatment and genetic counseling of the disease.

关 键 词：中枢性甲状腺功能减退 IGSF1基因 新生儿筛查 促甲状腺素 

分 类 号：R581.2[医药卫生—内分泌]