1例儿童Wolfram综合征并新发现的WFS1基因突变位点分析  

Novel Mutation of WFS1 Gene in One Pediatric Case of Wolfram Syndrome

作　　者：贾实磊[1] 陈仁典[1] 高晓洁[1] 陈冉冉[1] 倪芬芬[1] 南晓娟 郭建群[1] Jia Shilei;Chen Rendian;Gao Xiaojie;Chen Ranran;Ni Fenfen;Nan Xiaojuan;Guo Jianqun(Shenzhen Children’s Hospital,Guangdong Shenzhen 518026,China)

机构地区：[1]深圳市儿童医院,广东深圳518026

出　　处：《儿科药学杂志》2023年第8期35-37,共3页Journal of Pediatric Pharmacy

基　　金：深圳市高水平医院建设专项经费资助项目,编号SZGSP012。

摘　　要：目的:分析儿童Wolfram综合征(WS)的基因型和临床特点。方法:回顾性总结分析1例WS患儿的临床资料及基因检测结果。结果:患儿,男,16岁,2岁时在当地医院诊断“1型糖尿病”;8岁时因“视力进行性下降”行双眼白内障针吸+人工晶体植入术;11岁时诊断“尿崩症、神经源性膀胱、双侧输尿管扩张、肾积水”,予去氨加压片口服及间断导尿治疗,肾功能进行性恶化;15岁时进入终末期肾病,接受血液透析治疗;16岁时行异体肾移植,腹部输尿管造口排尿。现患儿经胰岛素泵给予门冬胰岛素控制血糖,醋酸去氨加压素片缓解多尿症状,他克莫司抗排斥治疗。基因检测显示,患儿WFS1基因纯合移码突变(c.14delC),导致氨基酸移码138位后提前终止(p.T5Mfs*138);父母验证为杂合突变。依据美国医学遗传学与基因组学学会(ACMG)指南,该突变为致病性突变,人类基因突变数据库(HGMD)未见报道,为新发现的突变位点。结论:WS为多系统受损疾病,进展快,预后差,极易误诊、漏诊。基因检测是确诊WS的重要依据。对于<10岁儿童发现有血糖异常伴视力或听力下降者应考虑此病并积极行基因筛查。本研究新发现1个WFS1基因纯合的移码突变位点,丰富了WFS1基因的突变谱。Objective:To analyze the genotype and clinical manifestations of Wolfram syndrome(WS)in children.Methods:Clinical data and genetic test results of one child with WS were retrospectively analyzed.Results:Male,16 years old,diagnosed with“type 1 diabetes mellitus”at the age of 2 years in the local hospital.At the age of 8 years,the child underwent cataract aspiration+intraocular lens implantation in both eyes due to“progressive vision loss”.At the age of 11 years,the child was diagnosed with“urolithiasis,neurogenic bladder,bilateral ureteral dilatation,and hydronephrosis”,and was treated with oral desmopressin tablets and intermittent catheterization,with progressive deterioration of renal function.The child developed end-stage renal disease at the age of 15 years and received hemodialysis treatment.At the age of 16 years,the child underwent allogeneic renal transplant,along with ureterostomy for urination.Insulin aspartate was given by insulin pump to control blood glucose,desmopressin acetate tablets to relieve polyuria symptoms,and tacrolimus anti-rejection therapy.Genetic tests showed homozygous frameshift mutation(c.14delC)in WFS1 gene,resulting in early termination of amino acid frameshift after 138 position(p.T5Mfs∗138).The parents’tests showed a heterozygous mutation.The mutation was pathogenic according to the American College of Medical Genetics(ACMG)guidelines.The mutation had not yet been reported in the Human Gene Mutation Database(HGMD)and involved a novel mutation site.Conclusion:WS is a disease with multi-system injury,rapid progression and poor prognosis,and is highly liable to misdiagnosis and missed diagnosis.Genetic testing is an important basis for confirming a diagnosis of WS.For children under 10 years of age presenting with blood glucose abnormality and vision or hearing loss,possibility of this disease should be considered and genetic screening should be proactively performed.This paper reports the discovery of a novel homozygous frameshift mutation in the WFS1 gene,and enric

关 键 词：基因突变 WFS1基因 WOLFRAM综合征 

分 类 号：R725.9[医药卫生—儿科]