核苷酸切除修复障碍16例临床特征及文献复习  

Clinical characteristics of 16 patients with nucleotide excision repair disorders and literature review

作　　者：胡丽竹 王静[2,3] 王秋红 杨舟[4] 黄昱[5] 高敬[2] 陈健 王彬[2] 刘蕊[2] 徐贤[6] 彭楠 王卉[8] 邓玉娇[9] 王丽强 陈海旭 马琳[4] 邹丽萍[2,3,11] Hu Lizhu;Wang Jing;Wang Qiuhong;Yang Zhou;Huang Yu;Gao Jing;Chen Jian;Wang Bin;Liu Rui;Xu Xian;Peng Nan;Wang Hui;Deng Yujiao;Wang Liqiang;Chen Haixu;Ma Lin;Zou Liping(Chinese People′s Liberation Army Medical School,Beijing 100853,China;Faculty of Pediatrics,Chinese People′s Liberation Army General Hospital,Beijing 100853,China;Department of Pediatrics,the First Medical Center of Chinese People′s Liberation Army General Hospital,Beijing 100853,China;Department of Dermatology,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China;Department of Medical Genetics,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China;Department of Radiology,the First Medical Center of Chinese People′s Liberation Army General Hospital,Beijing 100853,China;National Clinical Research Center for Geriatric Diseases,Chinese People′s Liberation Army General Hospital,Beijing 100853,China;College of Otolaryngology Head and Neck Surgery,Chinese People′s Liberation Army General Hospital,Beijing 100853,China;Department of Ultrasound,the First Medical Center of Chinese People′s Liberation Army General Hospital,Beijing 100853,China;Department of Ophthalmology,the First Medical Center of Chinese People′s Liberation Army General Hospital,Beijing 100853,China;Beijing Institute for Brain Disorders,Center for Brain Disorders Research,Capital Medical University,Beijing 100069,China)

机构地区：[1]中国人民解放军医学院,北京100853 [2]中国人民解放军总医院儿科医学部,北京100853 [3]中国人民解放军总医院第一医学中心儿科,北京100853 [4]国家儿童医学中心,首都医科大学附属北京儿童医院皮肤科,北京100045 [5]北京大学医学部基础医学院医学遗传学系,北京100191 [6]中国人民解放军总医院第一医学中心放射诊断科,北京100853 [7]中国人民解放军总医院国家老年疾病临床研究中心,北京100853 [8]中国人民解放军总医院耳鼻咽喉头颈外科医学部,北京100853 [9]中国人民解放军总医院第一医学中心超声科,北京100853 [10]中国人民解放军总医院第一医学中心眼科,北京100853 [11]首都医科大学脑重大疾病研究中心,北京脑重大疾病研究院,北京100069

出　　处：《中华实用儿科临床杂志》2022年第22期1730-1735,共6页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家重点研发计划项目(2016YFC1000707、2017YFC0908402);国家老年疾病临床研究中心开放课题(NCRCG-PLAGH-2019004);首都卫生发展科研专项(首发2022-1-5081)。

摘　　要：目的总结核苷酸切除修复(NER)障碍患儿的临床特征及基因突变位点。方法回顾性分析2008年10月至2022年2月中国人民解放军总医院收治住院及2015年10月至2022年2月首都医科大学附属北京儿童医院门诊收治确诊的NER障碍患儿的临床资料,并对国内外已报道的中国病例进行文献复习。结果1.在16例NER障碍患儿中男6例,女10例;起病年龄为7.5(4.0,12.0)个月;确诊年龄为42.0(21.5,77.0)个月;包括3种类型:科凯恩综合征(CS)13例、着色性干皮病(XP)2例、眼-脑-面-骨综合征(COFS)1例;涉及4个致病基因,11例CSA、3例CSB、1例XPG、1例XPD。16例患儿以光过敏及发育落后起病,各型均有神经系统症状,XP及CS患儿均有皮肤症状。CS患儿有特殊面容、视听障碍、小头畸形、神经影像学特征改变。COFS伴宫内发育迟缓。2.文献复习结果:共检索到既往报道中国病例96例,共涉及6种类型,其中45例CS,44例XP,毛发低硫营养不良4例,COFS、XP-CS、紫外线敏感综合征各1例。涉及9种突变基因,33例CSA、15例XPA、13例CSB、10例XPV、9例XPC、7例XPG、7例XPD、1例XPF、1例MPLKIP。常见症状为生长发育障碍(62例)、皮肤光过敏(61例)、特殊面容(52例)、智力障碍(49例)、小头畸形(48例)等。33/36例(91.7%)影像学示基底核或苍白球钙化。3例在孕期有宫内发育迟缓、小头畸形等表现。结论妊娠期出现宫内发育迟缓、小头畸形及临床发现皮肤光过敏、特殊面容、生长发育落后、智力障碍、肌张力高、基底核钙化等异常者,应考虑NER相关疾病可能,应早期行相关基因检测进一步明确诊断。Objective To summarize the clinical manifestations and gene mutation features of patients with nucleotide excision repair(NER)disorders.Methods A retrospective analysis was made on clinical data of patients with NER disorders who were admitted to the Chinese People′s Liberation Army General Hospital from October 2008 to February 2022 and diagnosed in the Outpatient Department of Beijing Children′s Hospital,Capital Medical University from October 2015 to February 2022.Literature on previously reported Chinese patients with NER disorders was reviewed.Results(1)A total of 16 patients with NER disorders were enrolled,including 6 males and 10 females.The onset age was 7.5(4.0,12.0)months and the age at diagnosis was 42.0(21.5,77.0)months.There were 3 types of NER disorders:Cockayne syndrome(CS)in 13 cases,Xeroderma Pigmentosum(XP)in 2 cases and Cerebro-Oculo-Facio-Skeletal syndrome(COFS)in 1 case.Four disease-causing genes were detected:CSA gene in 11 cases,CSB gene in 3 cases,XPG gene in 1 case,and XPD gene in 1 case.The first symptoms of the 16 patients were photosensitivity and developmental delay,and neurological symptoms were observed in all the 3 NER disorder types.XP and CS patients had skin symptoms.CS patients presented typical facial features,visual and auditory impairment,microcephaly and changes in neuroimaging features.COFS patients showed intrauterine growth retardation.(2)Results of literature review:a total of 96 Chinese patients reported were retrieved,involving 6 disease types,including CS in 45 cases,XP in 44 cases,trichothiodystrophy in 4 cases,COFS in 1 case,XP-CS in 1 case,and ultraviolet sensitive syndrome in 1 case.Nine mutated genes were identified:CSA in 33 cases,XPA in 15 cases,CSB in 13 cases,XPV in 10 cases,XPC in 9 cases,XPG in 7 cases,XPD in 7 cases,XPF in 1 case,and MPLKIP in 1 case.The common symptoms were growth failure(62 cases),skin photosensitivity(61 cases),typical facial features(52 cases),mental retardation(49 cases)and microcephaly(48 cases).Among 36 cases had imaging data

关 键 词：核苷酸切除修复 科凯恩综合征 着色性干皮病 临床特征 基因突变 

分 类 号：R725.9[医药卫生—儿科]