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Human autosomal recessive osteopetrosis (ARO),also known as infantile malignant osteopetrosis,is a rare genetic bone disorder that often causes death.Mutations in T-cell immune regulator 1 (TCIRG1) are a frequent cause of human ARO.Six additional genes (TNFSF11,TNFRSF11A,CLCN7,OSTM1,SNX10,PLEKHM1) were also found to be associated with human ARO.In order to expand the mutation spectrum and clinical diversity for a better understanding of the ARO phenotype and to further investigate the clinical characteristics of benign subjects with ARO,we here report five individuals with ARO from four unrelated Chinese families.X-ray examination was conducted and bone tuover markers were assayed.The gene of T-cell immune regulator 1 (TCIRG1) was screened and analyzed.Monocyte-induced osteoclasts were prepared and their resorption ability was studied in vitro.We identified five novel mutations (c.66delC,c.1020+1_1020+5dup,c.2181C＞A,c.2236+6T＞G,c.692delA) in these patients.Four patients displayed a malignant phenotype,three of them died,and one who received bone marrow transplantation survived.The remaining one,a 24-year-old male from a consanguineous family,was diagnosed based on radiological findings but presented no neurological or hematological defects.He was homozygous for c.2236+6T＞G in intron 18;this mutation influenced the splicing process.An in vitro functional study of this novel splicing defect showed no resorption pits on dentine slices.TCIRG1-dependent osteopetrosis with a mild clinical course was observed for the first time in Chinese population.The present findings add to the wide range of phenotypes of Chinese patients with TCIRG1-dependent ARO and enrich the database of TCIRG1 mutations.