SAMD9/SAMD9L突变相关疾病5例并文献复习  

SAMD9/SAMD9L gene mutations associated diseases: analysis of 5 children and literature review

作　　者：王希楠 覃霞 姚如恩 金燕樑[3] 陈静[1] WANG Xinan;QIN Xia;YAO Ruen;JIN Yanliang;CHEN Jing(’1.Department of Hematology and Oncology,Shanghai 200127,China;Department of Rheumatology,Shanghai 200127,China;Department of Genetic Diagnostics,Shanghai Children′s Medical Center,School of Medicine,Shanghai Jiao Tong University,Shanghai 200127,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血液肿瘤科,上海200127 [2]上海交通大学医学院附属上海儿童医学中心风湿免疫科,上海200127 [3]上海交通大学医学院附属上海儿童医学中心分子遗传诊断科,上海200127

出　　处：《中国小儿血液与肿瘤杂志》2022年第4期221-225,共5页Journal of China Pediatric Blood and Cancer

摘　　要：目的总结分析SAMD9/SAMD9L基因突变所致疾病的临床特点和基因结果。方法回顾性分析2017年1月—2019年12月于上海交通大学医学院附属上海儿童医学中心诊断的5例SAMD9/SAMD9L基因突变相关疾病的患儿临床资料和全外显子组测序结果。结果5例患儿中男孩3例(2例为同胞兄弟),女孩2例,中位年龄2岁(9个月~9岁)。2例表现为骨髓衰竭,均用环孢素治疗有效,其中1例停药后复发,成功接受异基因造血干细胞移植;1例表现为全身型幼年特发性关节炎合并巨噬细胞活化综合征,免疫抑制治疗有效;2例同胞兄弟表现为神经系统发育落后,其中1例脑垂体拉克氏囊肿。全外显子组测序结果显示2例为SAMD9基因的移码突变,2例为SAMD9L基因的移码突变,1例为SAMD9L基因的错义突变,均为致病突变。4例突变来自父亲或母亲,1例为新发突变。结论SAMD9/SAMD9L基因突变所致疾病可涉及造血、免疫和神经等诸多系统,临床表现可从无明显临床症状到严重综合征。对于SAMD9/SAMD9L基因突变所致的骨髓衰竭性疾病,异基因造血干细胞移植是有效的治疗手段,对于诸如神经系统等其他系统的病变,则以对症支持治疗为主。Objective To analyze the clinical characteristics and gene results of SAMD9/SAMD9L gene mutation associated diseases.Methods Clinical features and whole exome sequencing results of 5 cases with SAMD9/SAMD9L gene mutations in Shanghai Children′s Medical Center from January 2017 to December 2019 were analyzed retrospectively.Results Among 5 cases,there were 3 males(2 siblings)and 2 females,with a median age of 2 years(range from 9 months to 9 years)old.Two patients presented with bone marrow failure,and responded to cyclosporine,one of whom relapsed after drug discontinuation and successfully underwent allogeneic hematopoietic stem cell transplantation.One patient had systemic juvenile idiopathic arthritis with macrophage activation syndrome,which responded to immunosuppressive therapy.Two siblings presented with neurodevelopmental retardation,including one with Rathke′s cleft cyst.By analysis of whole exome sequencing,2 frameshift mutations in SAMD9,2 frameshift mutations in SAMD9L,and 1 missense mutation in SAMD9L were found.Four of the mutations were from parents and one was a de novo mutation.Conclusions The diseases caused by SAMD9/SAMD9L gene mutations can involve many systems,including hematopoiesis,immunity,and neurology,with varied clinical characteristics range from no obvious symptoms to severe syndromes.Allogeneic hematopoietic stem cell transplantation is an effective treatment for bone marrow failure cases with SAMD9/SAMD9L gene mutations.For other system such as nervous system diseases,symptomatic supportive treatment is the main treatment.

关 键 词：SAMD9 SAMD9L 骨髓衰竭 幼年特发性关节炎 神经病变 

分 类 号：R725.9[医药卫生—儿科]