儿童铁粒幼红细胞贫血的临床特征及基因突变谱分析  

Clinical features and gene mutation spectrum in children with sideroblastic anemia

作　　者：安文彬 刘超 万扬 郭晔 王书春 张英驰 竺晓凡 AN Wen-Bin;LIU Chao;WAN Yang;GUO Ye;WANG Shu-Chun;ZHANG Ying-Chi;ZHU Xiao-Fan(Pediatric Blood Diseases Centre,Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,Tianjin 300020,China)

机构地区：[1]中国医学科学院北京协和医学院血液病医院(血液学研究所)儿童血液病诊疗中心,天津300020 [2]实验血液学国家重点实验室,天津300020

出　　处：《中国当代儿科杂志》2019年第10期1016-1021,共6页Chinese Journal of Contemporary Pediatrics

基　　金：国家自然科学基金（81700109）;协和青年科研基金&中央高校基本科研业务费专项资金（2017320024）;国家重点研发计划（2016YFC0901503）;爱佑慈善基金

摘　　要：目的对铁粒幼红细胞贫血(SA)患儿的临床特征和基因突变谱进行分析,探讨目的基因捕获二代测序技术在SA患儿分子诊断中的临床应用价值,提高对SA的早期诊断和临床干预水平。方法收集36例诊断为SA患儿的临床资料,采用目的基因捕获二代测序方法进行SA相关致病基因、与血红素合成及线粒体铁代谢有关的基因检测,分析基因型与临床表型的关系。结果36例患儿中,32例为遗传性铁粒幼红细胞贫血(CSA),4例为骨髓增生异常综合征伴环形铁粒幼红细胞(MDS-RS)。共53%(19/36)患儿检测到CSA相关基因突变,其中ALAS2基因突变占47%(9/19),SLC25A38基因突变占21%(4/19),线粒体片段缺失占32%(6/19)。所有MDS-RS患儿均未检测到致病/可能致病性基因突变。89%(17/19)为已知致病突变,11%(2/19)为新变异。ALAS2基因新变异c.1153A>T(p.I385F)评级为"可能致病的"及SLC25A38基因新变异c.175C>T(p.Q59X)评级为"致病的"。结论儿童CSA以ALAS2及SLC25A38基因突变为主,但线粒体基因片段缺失亦占有相当比例,对于婴儿期即出现的低增生性贫血,需考虑线粒体病的可能。Objective To study the clinical features and gene mutation spectrum of children with sideroblastic anemia (SA) and the clinical value of targeted next-generation sequencing in the molecular diagnosis of children with SA.Methods Clinical data were collected from 36 children with SA. Targeted next-generation sequencing was used to detect mutations in SA-related pathogenic genes and genes associated with heme synthesis and mitochondrial iron metabolism. The association between genotype and clinical phenotype was analyzed.Results Of the 36 patients, 32 had congenital sideroblastic anemia (CSA) and 4 had myelodysplastic syndrome with ring sideroblasts (MDS-RS). Mutations in CSA-related genes were detected in 19 children (19/36, 53%), among whom 9 (47%) had ALAS2 mutation, 4 (21%) had SLC25A38 mutation, and 6 (32%) had mitochondrial fragment deletion. No pathogenic gene mutation was detected in 4 children with MDS-RS. Among the 19 mutations, 89%(17/19) were known mutations and 11%(2/19) were novel mutations. The novel mutation of the ALAS2 gene c.1153A >T(p.I385F) was rated as "possibly pathogenic" and the novel mutation of the SLC25A38 gene c.175C > T(p.Q59X) was rated as "pathogenic".Conclusions ALAS2 and SLC25A38 gene mutations are commonly seen in children with CSA, but mitochondrial gene fragment deletion also accounts for a relatively high proportion. For children with hypoplastic anemia occurring in infancy, mitochondrial disease should be considered.

关 键 词：遗传性铁粒幼红细胞贫血 骨髓增生异常综合征伴环形铁粒幼红细胞 临床特征 基因突变 目的基因捕获二代测序 儿童 

分 类 号：R725.7[医药卫生—儿科]