To identify candidate pathogenic genes of early-stage Crohn’s disease (CD) and predict potential roles of genetic factors in CD, we performed whole exome sequencing on a child with early-stage Crohn’s disease (CD) and her parents (core family), found that the patient carried heterozygous variants of 4 genes: NOD2 c. 2257 C>T, IL10RA c. 301 C>T, PLA2G6 c. 2029 C>T, COL7A1 c. 3190 G>A. With joint action of NOD2, IL10RA, PLA2G6 and COL7A1, excessive intestinal inflammatory response is triggered, resulting in normal intestinal wall tissue damage. Meanwhile, intestinal wall tissue repair is impaired, aggravating inflammation and injury, and leading to severe CD phenotype.