ArticleGut2016
Congenital secretory diarrhoea caused by activating germline mutations in GUCY2C.
Article in Gut, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 97 citations in OpenAlex.
- Bioactivity of Oral Linaclotide in Human Colorectum for Cancer Chemoprevention.Cancer prevention research (Philadelphia, Pa.) · 2017Trial
- Therapeutic zinc targets dysregulated GC-C signaling and restores ileal defects in a preclinical model of familial diarrheal disease.American journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Monogenic forms of inflammatory bowel disease: Genetic mechanisms, models, and clinical implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- A biochemical difference between HAI-2 variants causing syndromic and non-syndromic Congenital Sodium Diarrhea.PloS one · 2026Article
- Congenital Diarrhea: A Case Report on Challenges in Both Prenatal and Postnatal Diagnosis.Case reports in obstetrics and gynecology · 2026Article
- De Novo GUCY2C and PRR12 Mutations in a Patient With Chronic Diarrhea, Small Bowel Obstructions, and Developmental Delay.ACG case reports journal · 2025Article
- Zinc inhibits cAMP-induced ClAmerican journal of physiology. Cell physiology · 2025Article
- Gut reactions and gut instincts: regulation of intestinal homeostasis by receptor guanylyl cyclase C (GC-C).The Biochemical journal · 2025Review
- Pathogenic Deep Intronic PCSK1 Variant Causes Proprotein Convertase 1/3 Deficiency in a Family.Clinical genetics · 2025Article
- Advances in Understanding Intestinal Homeostasis: Lessons from Inflammatory Bowel Disease and Monogenic Intestinal Disorder Pathogenesis.International journal of molecular sciences · 2025Review
- Congenital enteropathy caused by ezrin deficiency.Human genetics · 2025Article
- Congenital diarrhea and enteropathies caused by a heterozygous mutation in theFrontiers in pediatrics · 2025Article
- Diet management in congenital diarrheas and enteropathies - general concepts and disease-specific approach, a narrative review.The American journal of clinical nutrition · 2024Review
- Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments.Gastroenterology · 2024Review
- New functions and roles of the NaPflugers Archiv : European journal of physiology · 2024Review
- Calcium-sensing receptor activator cinacalcet for treatment of cyclic nucleotide-mediated secretory diarrheas.Translational research : the journal of laboratory and clinical medicine · 2024Article
- The genetics of monogenic intestinal epithelial disorders.Human genetics · 2023Review
- Congenital Sodium Diarrhea Caused by a Novel Spontaneous Mutation in the GUCY2C Gene.Indian journal of pediatrics · 2023Article
- Congenital sodium diarrhoea caused by rare de novo activating guanylate cyclase mutation.BMJ case reports · 2022Article
- Further delineation of SLC9A3-related congenital sodium diarrhea.Molecular genetics & genomic medicine · 2022Article
Corrections and comments
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Authors and funding
18 authors at 12 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveCongenital sodium diarrhoea (CSD) refers to a form of secretory diarrhoea with intrauterine onset and high faecal losses of sodium without congenital malformations. The molecular basis for CSD remains unknown. We clinically characterised a cohort of infants with CSD and set out to identify disease-causing mutations by genome-wide genetic testing.
designWe performed whole-exome sequencing and chromosomal microarray analyses in 4 unrelated patients, followed by confirmatory Sanger sequencing of the likely disease-causing mutations in patients and in their family members, followed by functional studies.
resultsWe identified novel de novo missense mutations in GUCY2C, the gene encoding receptor guanylate cyclase C (GC-C) in 4 patients with CSD. One patient developed severe, early-onset IBD and chronic arthritis at 4 years of age. GC-C is an intestinal brush border membrane-bound guanylate cyclase, which functions as receptor for guanylin, uroguanylin and Escherichia coli heat-stable enterotoxin. Mutations in GUCY2C were present in different intracellular domains of GC-C, and were activating mutations that enhanced intracellular cyclic guanosine monophosphate accumulation in a ligand-independent and ligand-stimulated manner, following heterologous expression in HEK293T cells.
conclusionsDominant gain-of-function GUCY2C mutations lead to elevated intracellular cyclic guanosine monophosphate levels and could explain the chronic diarrhoea as a result of decreased intestinal sodium and water absorption and increased chloride secretion. Thus, mutations in GUCY2C indicate a role for this receptor in the pathogenesis of sporadic CSD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.