Congenital diarrhea/enteropathy due to a novel biallelic PERCC1 variant - a case-based review and variant analysis

Congenital diarrhea/enteropathy due to inherited biallelic defects in the newly discovered gene PERCC1 has been reported in only a few patients thus far. We utilized whole-exome sequencing (WES) to identify a novel PERCC1 stop-gain variant (c.188C>G, p.Ser63*). Literature review identified 16 additional patients - 13 with large biallelic deletions involving the PERCC1 gene and three with a homozygous single-nucleotide (stop-gain) variant (c.390C>G, p.Tyr130*). Median [range] age at onset of diarrhea in patients with available data (including ours) is 9.5 [1-21] days. Chronic intractable diarrhea often results in growth failure, meriting the utilization of parenteral nutrition (PN), especially during the first few years of life. Discontinuation of PN has been reported in six patients at an age of 8 [4-17] years. Our report highlights the role of WES in identifying PERCC1 variants in patients with congenital diarrhea/enteropathy. Thus far, PERCC1 variants have primarily been identified through targeted testing or whole-genome sequencing.