Abstract:Abstract: Objective The clinical characteristics and genetic etiology of children in a family with osteosclerosis were analyzed by genetie testing to improve the understanding of clinicians on hereditary malignant osteosclerosis. Methods The biochemical indexes and genes of the children in the family were detected, combined with the medical history of the children, and the clinical symptoms of the disease were summarized. Genonic DNA from peripheral blood of the children and their parents was extracted, and the whole-exome high-throughput sequencing was used for gene detection. Sanger sequencing was used to further verify the mutation sites, and the data were analyzed. Results Whole exome sequencing combined with Sanger sequencing venified that the homozygous CT dinucleotide insertion of TCIRGI in exon 5 C493. _T494, which is resulted in the code shift mutation of TCIRGI. According to the recommendations of the American Society of Medical Genetics and Genomics ( ACMG) guidelines and the ClinGen Group of Experts on the application of the guidelines ,it was suggested that the C.493_ 494DUP mutation of TCIRGI was a pathogenie mutation, which is related to the autosomal recessive genetic disease Osteopetrosis, autosomal recessive I . Conclusion The exon of the TCIRG1 gene has been mutated ,leading to the risk of bone sclerosis typeI autosomal recessive genetic disease,the mutation c.493_ 494dup is a new type of mutation.The dentification of mutations is helpful to the diagnosis of the disease of the child and the prenatal diagnosis of the parents when they give birth again, which is conducive to healthy birth and good care, improve the family happiness and reduce the social burden.