中国范科尼贫血诊断现状及遗传学特征分析  

Diagnosis status and genetic characteristics analysis of Fanconi anemia in China

作　　者：李牛[1] 胡昳歆 覃霞 朱易萍 周铭[5] 何兰 常丽贤 徐晓军[8] 代艳[9] 曹星玉 陈凯 王红美[12] 王春静 何岳林[14] 钱晓文 许兰平[16] 陈静[3] Li Niu;Hu Yixin;Qin Xia;Zhu Yiping;Zhou Ming;He Lan;Chang Lixian;Xu Xiaojun;Dai Yan;Cao Xingyu;Chen Kai;Wang Hongmei;Wang Chunjing;He Yuelin;Qian Xiaowen;Xu Lanping;Chen Jing(Department of Medical Genetics and Molecular Diagnostic Laboratory,Shanghai Children′s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Department of Hematology,Children′s Hospital of Soochow University,Suzhou 215000,China;Department of Hematology and Oncology,Shanghai Children′s Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China;Department of Pediatrics,West China Second University Hospital of Sichuan University,Chengdu 610041,China;Department of Hematology,Guangzhou First People′s Hospital,Guangzhou 510030,China;Nanfang-Chunfu Children′s Institute of Hematology&Oncology,Dongguan 523000,China;Department of Pediatrics,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjing 300020,China;Department of Hematology and Oncology,Children′s Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China;Department of Pediatrics,People′s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,China;Department of Transplantation,Hebei Yanda Ludaopei Hospital,Langfang,065201,China;Department of Hematology and Oncology,Shanghai Children′s Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200040,China;Department of Pediatrics,the First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan Hospital,Jinan 250014,China;Department of Hematology,Shenzhen Children′s Hospital,Shenzhen 518028,China;Department of Pediatrics,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;Department of Hematology,Children′s Hospital of Fudan University,Shanghai 201102,China;Department of Hematology,Peking University People′s Hospital,Beijing 100044,China)

机构地区：[1]上海交通大学医学院附属上海儿童医学中心遗传分子诊断科,上海200127 [2]苏州儿童医院血液科,苏州215000 [3]上海交通大学医学院附属上海儿童医学中心血液肿瘤科,上海200127 [4]四川大学华西第二医院儿科,成都610041 [5]广州市第一人民医院血液科,广州510030 [6]南方春富(儿童)血液病研究院,东莞523000 [7]中国医学科学院血液病医院(中国医学科学院血液学研究所)儿科,天津300020 [8]浙江大学医学院附属儿童医院血液肿瘤中心,杭州310003 [9]广西壮族自治区人民医院儿科,南宁530021 [10]河北燕达陆道培医院移植科,廊坊065201 [11]上海交通大学医学院附属上海市儿童医院血液肿瘤科,上海200040 [12]山东第一医科大学第一附属医院(山东省千佛山医院)小儿内科,济南250014 [13]深圳儿童医院血液肿瘤科,深圳518028 [14]南方医科大学南方医院儿科,广州510515 [15]复旦大学附属儿科医院血液科,上海201102 [16]北京大学人民医院血液科,北京100044

出　　处：《中华儿科杂志》2023年第10期889-895,共7页Chinese Journal of Pediatrics

基　　金：申康新兴前沿联合攻关项目(SHDC12014118);上海市“科技创新行动计划”医学创新研究专项(20MC1920400)。

摘　　要：目的分析中国范科尼贫血(FA)的临床特征和分子诊断现状。方法回顾性分析中国造血干细胞移植和中国儿童造血干细胞移植登记组2009年8月至2022年1月收录的107例FA患儿的一般情况、临床特征以及染色体断裂实验和基因检测结果;根据变异类型将FANCA基因突变患儿分为轻型和重型突变组,并采用Wilcoxon秩和检验比较组间表型差异。结果176例登记FA患儿中,69例(39.2%)因缺乏明确的基因诊断结果而被剔除,余来自15家医院的107例患儿纳入本研究,包括男70例、女37例,移植治疗年龄6(4,9)岁。入组患儿涉及10个致病基因,包括89例FANCA基因、7例FANCG基因、3例FANCB基因、2例FANCE基因以及FANCC、FANCD1、FANCD2、FANCF、FANCJ和FANCN基因各1例;69.2%(72/104)的患儿表现为复合杂合或纯合功能丧失型变异。FANCA基因变异中79.2%(141/178)为功能丧失型变异,且外显子大缺失占比20.8%(37/178)。51.4%的患儿(55/107)有染色体断裂检测记录,阳性率81.8%(45/55)。80例患儿的172个先天性畸形中,牛奶咖啡斑(16.3%,28/172)、拇指畸形(16.3%,28/172)、多指(13.9%,24/172)和矮小(12.2%,21/172)是FA患儿较常见的先天性畸形。50例重型与26例轻型FANCA基因突变突变患儿相比,先天性畸形数差异无统计学意义(Z=-1.33,P=0.185)。结论FANCA基因是FA患儿最主要的致病基因,临床需加强对其外显子缺失的检测,不同FANCA基因变异类型患儿之间未见表型差异;染色体断裂检测有助于变异致病性判定,但其精准性有待提升。ObjectiveTo analyze the clinical and molecular diagnostic status of Fanconi anemia(FA)in China.MethodsThe General situation,clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group(CBMTRG)and the Chinese Children Blood and Marrow Transplantation Registry Group(CCBMTRG)from August 2009 to January 2022 were analyzed retrospectively.Children with FANCA gene variants were divided into mild and severe groups based on the type of variant,and Wilcoxon-test was used to compare the phenotypic differences between groups.ResultsOf the 176 registered FA patients,69(39.2%)cases were excluded due to lack of definitive genetic diagnosis results,and the remaining 107 children from 15 hospitals were included in the study,including 70 males and 37 females.The age at transplantation treatment were 6(4,9)years.The enrolled children were involved in 10 pathogenic genes,including 89 cases of FANCA gene,7 cases of FANCG gene,3 cases of FANCB gene,2 cases of FANCE gene and 1 case each of FANCC,FANCD1,FANCD2,FANCF,FANCJ,and FANCN gene.Compound heterozygous or homozygous of loss-of-function variants account for 69.2%(72/104).Loss-of-function variants account for 79.2%(141/178)in FANCA gene variants,and 20.8%(37/178)were large exon deletions.Fifty-five children(51.4%)had chromosome breakage test records,with a positive rate of 81.8%(45/55).There were 172 congenital malformations in 80 children.Café-au-Lait spots(16.3%,28/172),thumb deformities(16.3%,28/172),polydactyly(13.9%,24/172),and short stature(12.2%,21/172)were the most common congenital malformations in Chinese children with FA.No significant difference was found in the number of congenital malformations between children with severe(50 cases)and mild FANCA variants(26 cases)(Z=-1.33,P=0.185).ConclusionsFANCA gene is the main pathogenic gene in children with FA,where the detection of its exon deletion should be strengthened clinically.There were no phenotypic dif

关 键 词：范科尼贫血 儿童 基因 染色体断裂 

分 类 号：R725.5[医药卫生—儿科]