Genotype-phenotype correlations in EPCAM-associated congenital tufting enteropathy: a case report and systematic
Liqian Zhao1, Yucan Zheng1, Hao Liu2
1Department of Gastroenterology, Children's Hospital of Nanjing Medical University, Nanjing, China.
Background:
Congenital tufting enteropathy (CTE) is a rare autosomal-recessive enteropathy caused by EPCAM variants. While the clinical spectrum ranges from intractable diarrhea to manageable outcomes, the genotype-phenotype correlation remains undefined.
Methods:
We report a case of an infant diagnosed with CTE carrying a novel frameshift variant (c.315delT), and present a systematic review of previously published molecularly confirmed cases. Genotypes were stratified into truncating (nonsense, frameshift, large deletions) and non-truncating (missense, splicing, in-frame indel) groups to assess their impact on intestinal failure severity.
Results:
The index patient, carrying a homozygous truncating variant, presented with severe malnutrition and intestinal failure. In the pooled cohort (n = 150), truncating variants were significantly associated with dependency on total parenteral nutrition (TPN) compared to non-truncating variants (OR 2.37, 95% CI 1.15-4.90, p = 0.020). Sensitivity analysis supported this association (OR 2.42, 95% CI 1.07-5.47, p = 0.045). Geographically, truncating variants were enriched in the Eastern Mediterranean Region (OR 9.32, p < 0.001).
Conclusions:
Truncating EPCAM variants showed a preliminary but significant clinical association with severe intestinal failure requiring TPN. These findings support early risk stratification for aggressive nutritional management but warrant further validation in prospective cohorts.
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