Abstract: 　Objective　To investigate the clinical features and genetic change of Omenn syndrome. Method　Clinical data of two sporadic patients with Omenn syndrome and their family members were collected, and next generation sequencing was used to analyze immunodeficiency associated genes. Results　Two patients (one boy and one girl) had a history of recurrent infection and skin rash. The level of IgA, IgM and IgG was decreased. Both of them have a lower level of CD8+ T lymphocytes and CD19+ B lymphocytes, but the number of NK cells increased. Sequencing found a homozygous mutation (c.1211G>A) in RAG1 gene in the girl, and both her father and mother were heterogeneous carrier of this mutation. In the boy, we found novel compound heterozygous mutations, c.830A>G and c.104G>C in RAG2R gene, inherited from his mother and father, respectively. Bioinformatics predicts that these two mutations are likely to be pathogenic. Conclusions　The age of Omenn syndrome onset was earlier, with compromised immunological function. Gene detection was helpful for early diagnosis. We found that two novel mutations in RAG2R could cause Omenn syndrome.