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.