伴髓系恶性转化的Shwachman-Diamond综合征患儿的临床特征及基因突变分析  

Clinical features and gene mutations of children with Shwachman-Diamond syndrome and malignant myeloid transformation

作　　者：安文彬 刘超 万扬 常丽贤 陈晓燕 竺晓凡 AN Wen-Bin;LIU Chao;WAN Yang;CHANG Li-Xian;CHEN Xiao-Yan;ZHU Xiao-Fan(State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China)

机构地区：[1]中国医学科学院血液病医院(中国医学科学院血液学研究所),天津300020 [2]实验血液学国家重点实验室,天津300020 [3]国家血液病临床医学研究中心,天津300020

出　　处：《中国当代儿科杂志》2020年第5期460-465,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);爱佑慈善基金。

摘　　要：目的探讨伴髓系恶性转化的Shwachman-Diamond综合征(SDS)患儿的临床特征及基因突变情况。方法采用二代测序方法检测11例伴髓系恶性转化的SDS患儿的基因突变情况,分析患儿的临床特征和基因突变谱。结果11例SDS患儿中,9例(82%)表现为儿童难治性血细胞减少(RCC),1例(9%)为骨髓增生异常综合征(MDS)伴原始细胞增多(MDS-EB),1例(9%)为急性髓系白血病伴MDS相关改变(AML-MRC)。发生髓系恶性转化的中位年龄为48个月(范围:7个月~14岁)。5例(45%)患儿表现为单纯的血液系统异常。所有患儿均检测到SBDS基因突变,常见的突变形式为c.258+2T>C纯合突变(5例,45%)和c.184A>T+c.258+2T>C复合杂合突变(3例,27%)。SBDS基因新变异c.634_635insAACATACCTGT+c.637_638delGA和c.8T>C分别评级为“致病的”和“可能致病的”。转化为RCC和MDS-EB/AML-MRC的患儿3年预期总体生存率分别为100%、0%(P=0.001)。结论SDS患儿可能以血液系统症状为唯一表现,临床应引起重视。恶性转化的类型与预后相关。Objective To study the clinical features and genetic mutations of children with Shwachman-Diamond syndrome(SDS)and malignant myeloid transformation.Methods Next-generation sequencing was used to analyze the gene mutations in 11 SDS children with malignant myeloid transformation,and their clinical features and genetic mutations were analyzed.Results Of the 11 children with SDS,9(82%)presented with refractory cytopenia of childhood(RCC),1(9%)had myelodysplastic syndrome with excess blasts(MDS-EB),and 1(9%)had acute myeloid leukemia with myelodysplasia-related changes(AML-MRC).The median age of onset of malignant myeloid transformation was 48 months(ranged 7 months to 14 years).Of the 11 children,45%had abnormalities in the hematological system alone.Mutations of the SBDS gene were detected in all 11 children,among whom 5(45%)had c.258+2T>C homozygous mutation and 3(27%)had c.184A>T+c.258+2T>C compound heterozygous mutation.The new mutations of the SBDS gene,c.634_635insAACATACCTGT+c.637_638delGA and c.8T>C,were rated as“pathogenic”and“possibly pathogenic”respectively.The 3-year predicted overall survival rates of children transformed to RCC and MDS-EB/AML-MRC were 100%and 0%respectively(P=0.001).Conclusions SDS children may have hematological system symptoms as the only manifestation,which needs to be taken seriously in clinical practice.The type of malignant transformation is associated with prognosis.

关 键 词：Shwachman-Diamond综合征 骨髓增生异常综合征 急性髓系白血病 儿童 

分 类 号：R725.5[医药卫生—儿科]