关键词: Hematopoietic stem cell transplantation, Infantile malignant osteopetrosis, TCIRG1 gene, TCIRG1基因, 婴儿恶性石骨症, 造血干细胞移植

Abstract: Objective:To explore the clinical characteristics, pathogenicity gene, treatment and prognosis of infantile malignant osteopetrosis(IMO). Methods:The clinical data of one case with IMO was analyzed, and the second-generation high-throughput gene sequencing was applied for the infant and their parents to identify the causative mutation. To summarize the clinical features of the disease and the causative genes, the relevant literature was reviewed. Results:The X-ray showed the bone density of the child was increased. The high-throughput gene sequencing showed two compound heterozygous mutations of TCIRG1 gene in the child. One was nonsense mutation c.1360C>T(p.R454X) , and the other was frame shift mutation c.722delC(p.T241fs). The clinical diagnosis of IMO was established. A total of 238 cases with IMO were reported up to now, 128 cases from China(including one case of this study), and 110 cases abroad. The clinical characteristics were anemia(65.1%), hepatosplenomegaly(48.3%), visual impairment (47.9%),growth retardation(40%), thromboeytopenia(26.5%), infection(22.3%), skull abnormalities(17.2%), hypocalcemia(14.3%) , hydrocephalus(10.5%) and seizures(5.2%). Gene sequencing of 77 (58 cases from abroad and 19 cases from China) showed six pathogenic genes, including TCIRG1(50.6%), RANK and RANKL(18.2%), SNXIO(18.2%), OSTMl(7.8%) and CNCL7(5.2%), and all 19 cases from China showed TCIRG1 gene mutation. Hematopoietic stem cell transplantation was carried out in 64 cases, however, 16 patients died after transplantation. Conclusion:Anemia, hepatosplenomegaly and visual impairment are the main clinical symptoms of IMO. TCIRG1 mutation is the leading cause of IMO. We reported an novel heterozygous mutation of TCIRG1 gene causing IMO. Above results may enrich the mutation spectrum of TCIRG1 gene and provide new evidence for the molecular basis of IMO.