Abstract:  Objective To explore the clinical features and diagnosis of primary immunodeficiency disease caused by Tyk2 gene mutations. Methods Clinical data from the first case in China diagnosed of primary immunodeficiency disease caused by Tyk2 gene mutation were retrospectively analyzed, and related literature was reviewed. Results One year and 3 month old boy suffered with repeated pulmonary infection, chronic otitis media, intractable eczema like rash, repeated skin abscess, HSV infection, intracellular bacterial infection, and remarkedly increased total IgE. It was detected that compound heterozygous mutations of c.2269C ＞ G in No. 16 exon and c.149delC in No. 3 exon in Tyk2 gene. Literature searching found other 8 cases (5 males and 3 females) of immune deficiency patients caused by Tyk2 gene defects, all of which had Tyk2 gene homozygous mutations and presented with repeated infection of paranasal sinus and lung. In the 8 cases 6 cases were combined with mycobacterium tuverculosis infection, 4 cases had repeated virus infection, 4 cases had meningonecephalitis, 3 cases had intractable eczema like rash, 2 cases had salmonella enteritis, 1 case had remarkedly increased total IgE, one case had elevated eosinophils, 5 cases were born in intermarriage family and 1 case died of meningitis caused by unknown etiology. Conclusions When patients have repeated paranasal sinus infection and lung infection, combined with intracellular bacterial infection (including mycobacterium tuberculosis infection), and repeated virus infection or intractable eczema like rash, with or without increased total IgE, immunodeficiency disease caused by Tyk2 gene defection should be considered. Gene sequence analysis can assist in early diagnosis.