Major histocompatibility complex (MHC) II deficiency is a rare primary immunodeficiency disorder which is characterized by the deficiency of MHC class II molecules. The disease is caused by transcription factor mutations including class II transactivator (CIITA), regulatory factor X-5 (RFX5), RFX associated protein (RFXAP) and RFXAP containing ankyrin repeat (RFXANK), respectively. Mutations in the RFXANK gene account for more than 70% of all known patients worldwide. Herein, we reported a 10-month-old boy with MHC II deficiency caused by a novel mutation in RFXANK gene (c.337+1G>C) The boy was admitted to the hospital due to pneumonia and diarrhea at four months of age. Genetic analysis revealed a novel homozygous mutation in the RFXANK gene which derived from the c.337+1G>C heterozygous mutations in the RFXANK gene of his parents. The boy died 3 months after the diagnosis. More than 200 cases have been reported; and literature review revealed different mutation rates of four transcription factors in different countries or regions. This is the first case report of MHC II deficiency from East Asia. We also described all gene mutations which causing MHC II deficiency and epidemiology of MHC II deficiency with gene mutations in this paper.