Synergistic effects of Heterozygous variants of NOD2, IL10RA, PLA2G6 and
COL7A1 causative an extreme early-onset and severe Crohn's disease
Abstract
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.