ArticleAmerican journal of human genetics2018
Neonatal-Onset Chronic Diarrhea Caused by Homozygous Nonsense WNT2B Mutations.
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- LEF1 gene mutation impairs the intestinal barrier and causes diarrhea.Molecular and cellular pediatrics · 2026Article
- Loss of WNT2B Increases Tumor Burden and Malignant Features in Colorectal Cancer.Cancer communications (London, England) · 2026Article
- Necrotizing enterocolitis causes increased ileal goblet cell loss inbioRxiv : the preprint server for biology · 2025Article
- Loss of WNT2B Results in Epithelial Defects and Predisposes to Gastrointestinal Dysplasia in Humans.Cellular and molecular gastroenterology and hepatology · 2025Article
- Cellular and molecular basis of proximal small intestine disorders.Nature reviews. Gastroenterology & hepatology · 2024Review
- Non-canonical Wnt signaling triggered by WNT2B drives adrenal aldosterone production.bioRxiv : the preprint server for biology · 2024Article
- The genetics of monogenic intestinal epithelial disorders.Human genetics · 2023Review
- Transplanted human intestinal organoids: a resource for modeling human intestinal development.Development (Cambridge, England) · 2023Article
- Article
- Update on Biology and Genomics of Adrenocortical Carcinomas: Rationale for Emerging Therapies.Endocrine reviews · 2022Article
- Intestinal Wnt in the transition from physiology to oncology.World journal of clinical oncology · 2022Review
- Intestinal immunoregulation: lessons from human mendelian diseases.Mucosal immunology · 2021Review
- Article
- Novel variants in the stem cell niche factor WNT2B define the disease phenotype as a congenital enteropathy with ocular dysgenesis.European journal of human genetics : EJHG · 2021Article
- Epithelial WNT2B and Desert Hedgehog Are Necessary for Human Colonoid Regeneration after Bacterial Cytotoxin Injury.iScience · 2020Article
- AP1S1 missense mutations cause a congenital enteropathy via an epithelial barrier defect.Human genetics · 2020Article
- Clinical and genetic spectrum of children with congenital diarrhea and enteropathy in China.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Homozygous nonsense mutations in WNT2B were identified in three individuals from two unrelated families with severe, neonatal-onset osmotic diarrhea after whole-exome sequencing was performed on trios from the two families. Intestinal biopsy samples from affected individuals were used for histology and immunofluorescence and to generate enteroids ex vivo. Histopathologic evaluation demonstrated chronic inflammatory changes in the stomach, duodenum, and colon. Immunofluorescence demonstrated diminished staining for OLFM4, a marker for intestinal stem cells (ISCs). The enteroids generated from WNT2B-deficient intestinal epithelium could not be expanded and did not survive passage. Addition of CHIR-99021 (a GSK3A and GSK3B inhibitor and activator of canonical WNT/β-CATENIN signaling) could not rescue WNT2B-deficient enteroids. Addition of supplemental recombinant murine WNT2B was able to perpetuate small enteroids for multiple passages but failed to expand their number. Enteroids showed a 10-fold increase in the expression of LEF1 mRNA and a 100-fold reduction in TLR4 expression, compared with controls by quantitative RT-PCR, indicating alterations in canonical WNT and microbial pattern-recognition signaling. In summary, individuals with homozygous nonsense mutations in WNT2B demonstrate severe intestinal dysregulation associated with decreased ISC number and function, likely explaining their diarrheal phenotype. WNT2B deficiency should be considered for individuals with neonatal-onset diarrhea.
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Registered trials
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