摘要
目的分析儿童骨硬化症(osteopetrosis,OPT)的临床和遗传学特征。方法回顾性分析2015年5月—2024年3月收治的14例OPT患儿的临床资料,采用全外显子组测序技术检测OPT相关致病基因,并总结临床表型和基因型特点。结果14例患儿,男性10例,女性4例,中位就诊年龄8个月。OPT患儿临床表现主要为全身性骨硬化(14例,100%)、贫血(12例,86%)、感染(10例,71%)、血小板减少(9例,64%)、肝脾大(8例,57%)和发育迟缓(5例,36%)等。恶性型OPT(malignant osteopetrosis,MOP)患儿的血小板计数、肌酸激酶同工酶和血钙低于非MOP患儿,而白细胞计数、乳酸脱氢酶和碱性磷酸酶高于非MOP患儿(P<0.05)。12例患儿完成基因检测,共检出15种变异,CLCN7基因变异8个(53%),TCIRG1基因变异6个(40%),TNFRSF11A基因变异1个(7%)。CLCN7基因发现3个新位点变异,为c.2351G>C、c.1215-43C>T和c.1534G>A。4例TCIRG1基因型患儿的临床表型均为MOP。7例CLCN7基因型患儿中,中间型OPT 4例,良性型OPT 2例,MOP 1例。结论OPT患儿的临床表型具有异质性,基因型以CLCN7和TCIRG1基因变异为主,临床表型与基因型之间有一定关联。
Objective To study the clinical and genetic characteristics of osteopetrosis(OPT)in children.Methods A retrospective analysis was performed on the clinical data of 14 children with OPT.Whole-exome sequencing was used to detect pathogenic genes,and clinical phenotypes and genotypic features were summarized.Results Among the 14 children(10 males and 4 females),the median age at diagnosis was 8 months.Clinical manifestations included systemic osteosclerosis(14 cases,100%),anemia(12 cases,86%),infections(10 cases,71%),thrombocytopenia(9 cases,64%),hepatosplenomegaly(8 cases,57%),and developmental delay(5 cases,36%).Malignant osteopetrosis(MOP)cases had lower platelet counts,creatine kinase isoenzyme,and serum calcium levels,but higher white blood cell counts,lactate dehydrogenase,and alkaline phosphatase levels compared to non-MOP cases(P<0.05).Genetic testing identified 15 variants in 12 patients,including 8 variants in the CLCN7 gene(53%),6 in the TCIRG1 gene(40%),and 1 in the TNFRSF11A gene(7%).Three novel CLCN7 variants were identified:c.2351G>C,c.1215-43C>T,and c.1534G>A.All four patients with TCIRG1 variants exhibited MOP clinical phenotypes.Of the seven patients with CLCN7 variants,4 presented with intermediate OPT,2 with benign OPT,and 1 with MOP.Conclusions Clinical phenotypes of OPT in children are heterogeneous,predominantly involving CLCN7 and TCIRG1 gene variants,with a correlation between clinical phenotypes and genotypes.
作者
王敏
江傲霜
朱成琳
汪洁
王亚萍
高珊
李艳
陈天平
刘洪军
汪俭
WANG Min;JIANG Ao-Shuang;ZHU Cheng-Lin;WANG Jie;WANG Ya-Ping;GAO Shan;LI Yan;CHEN Tian-Ping;LIU Hong-Jun;WANG Jian(Department of Hematology and Oncology,Anhui Provincial Children's Hospital,Hefei 230022,China)
出处
《中国当代儿科杂志》
北大核心
2025年第5期568-573,共6页
Chinese Journal of Contemporary Pediatrics
基金
安徽省卫生健康科研项目(AHWJ2023BBa20030)。
