Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021831 (enteropathy)
 4,403 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine (CNSU). By whole-exome sequencing in five Japanese patients with CNSU and one unaffected individual, we found four candidate mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. The pathogenicity of the mutations was supported by segregation analysis and genotyping data in controls. By Sanger sequencing of the coding regions, 11 of 12 other CNSU patients and 2 of 603 patients with a diagnosis of Crohn's disease were found to have homozygous or compound heterozygous SLCO2A1 mutations. In total, we identified recessive SLCO2A1 mutations located at seven sites. Using RT-PCR, we demonstrated that the identified splice-site mutations altered the RNA splicing, and introduced a premature stop codon. Tracer prostaglandin E2 uptake analysis showed that the mutant SLCO2A1 protein for each mutation exhibited impaired prostaglandin transport. Immunohistochemistry and immunofluorescence analyses revealed that SLCO2A1 protein was expressed on the cellular membrane of vascular endothelial cells in the small intestinal mucosa in control subjects, but was not detected in affected individuals. These findings indicate that loss-of-function mutations in the SLCO2A1 gene encoding a prostaglandin transporter cause the hereditary enteropathy CNSU. We suggest a more appropriate nomenclature of "chronic enteropathy associated with SLCO2A1 gene" (CEAS).
...
PMID:A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter. 2653 16

Small intestinal ulcers include mucosal damage caused by drugs, particularly nonsteroidal anti-inflammatory drugs [NSAIDs], infectious diseases, and idiopathic inflammatory bowel disease. Previously, a group of Japanese investigators reported an unusual and uncommon type of enteritis and referred to the condition as chronic nonspecific multiple ulcers of the small intestine [CNSU]. CNSU is characterised by chronic blood and protein loss through persistent small intestinal ulcers. Recently, four candidate mutations in the solute carrier organic anion transporter family, member 2A1 [SLCO2A1] gene, encoding a prostaglandin transporter, were identified by whole-exome sequencing in patients with CNSU. However, because the name 'CNSU' was somewhat ambiguous, the more appropriate nomenclature of 'chronic enteropathy associated with the SLCO2A1 gene' [CEAS] has been suggested. CEAS ulcers are characterised by multiple, circular or eccentric oblique, shallow lesions with discrete margins. The most frequently affected site of CEAS is the ileum, in contrast to 'cryptogenic multifocal ulcerous stenosing enteritis [CMUSE]', for which the most frequent site is the jejunum. Impaired prostaglandin utilisation is thought to cause the small intestinal mucosal damage observed in CEAS, CMUSE, and NSAID-induced enteropathy. This review article focuses on endoscopic and clinical features of genetically diagnosed CEAS, accumulated in a nationwide survey, and illustrates the observations in the format of an atlas.
 ...
PMID:Chronic Enteropathy Associated With SLCO2A1 Gene [CEAS]-Characterisation of an Enteric Disorder to be Considered in the Differential Diagnosis of Crohn's Disease. 2851 Jun 89

The widespread use of capsule endoscopy and balloon-assisted endoscopy has provided easy access for detailed mucosal assessment of the small intestine. However, the diagnosis of rare small bowel diseases, such as cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), remains difficult because clinical and morphological features of these diseases are obscure even for gastroenterologists. In an issue of this journal in 2017, Hwang et al reviewed and summarized clinical and radiographic features of 20 patients with an established diagnosis of CMUSE. Recently, recessive mutations in the PLA2G4A and SLCO2A1 genes have been shown to cause small intestinal diseases. The small bowel ulcers in each disease mimic those in the other and furthermore those found in nonsteroidal anti-inflammatory drug-induced enteropathy. These recent and novel findings suggest that a clinical diagnosis exclusively based on the characteristics of small bowel lesions is possibly imprecise. Genetic analyses seem to be inevitable for the diagnosis of rare small bowel disorders such as CMUSE.
 ...
PMID:Genetic analysis is helpful for the diagnosis of small bowel ulceration. 2874 Mar 50

A case of chronic enteropathy associated with SLCO2A1 gene (CEAS) is presented. The female patient was readmitted four times during a three-year follow-up period for intractable dropsy and anemia. Multiple ulcers of small bowel wall were revealed by endoscopic examination. Computed tomography enterography (CTE) and magnetic resonance enterography (MRE) showed the segmental wall thickening of the small bowel. Hepatosplenomegaly and increased bone density of spine and pelvis suggested the diagnosis of myelofibrosis. X-ray films showed the cortical thickening of tibiofibula. The mutations of SLCO2A1 gene were revealed by gene test and the diagnosis of CEAS was confirmed. According to our case report, imaging examinations, including CTE, MRE and X-ray films provide additional valuable information during the diagnostic procedure of CEAS.
 ...
PMID:Chronic enteropathy associated with SLCO2A1 gene: A case report and literature review. 3119 8

Patients with chronic enteropathy associated with SLCO2A1 (CEAS) develop multiple circular, longitudinal, or eccentric ulcers in the ileum. It is sometimes difficult to distinguish CEAS from Crohn's disease. CEAS and primary hypertrophic osteoarthropathy (PHO) are together known to be caused by a mutation of SLCO2A1 gene. The case of a 65-year-old man whose characteristic appearance due to pachydermia of the forehead folds led to the diagnosis of CEAS with PHO is presented.
 ...
PMID:Characteristic Facial Appearance Was the Key to Diagnosing Chronic Enteropathy Associated with <i>SLCO2A1</i>-associated Primary Hypertrophic Osteoarthropathy. 3161 28

Chronic enteropathy associated with SLCO2A1 gene (CEAS) is caused by loss-of-function mutations in SLCO2A1, which encodes a prostaglandin (PG) transporter. In this study, we report a sibling case of CEAS with a novel pathogenic variant of the SLCO2A1 gene. Compound heterozygous variants in SLCO2A1 were identified in an 8-year-old boy and 12-year-old girl, and multiple chronic nonspecific ulcers were observed in the patients using capsule endoscopy. The splice site mutation (c.940 + 1G>A) of the paternal allele was previously reported to be pathogenic, whereas the missense variant (c.1688T>C) of the maternal allele was novel and had not yet been reported. The affected residue (p.Leu563Pro) is located in the 11th transmembrane domain (helix 11) of SLCO2A1. Because SLCO2A1 mediates the uptake and clearance of PGs, the urinary PG metabolites were measured by liquid chromatography coupled to tandem mass spectrometry. The urinary tetranor-prostaglandin E metabolite levels in the patients were significantly higher than those in unaffected individuals. We established cell lines with doxycycline-inducible expression of wild type SLCO2A1 (WT-SLCO2A1) and the L563P mutant. Immunofluorescence staining showed that WT-SLCO2A1 and the L563P mutant were dominantly expressed on the plasma membranes of these cells. Cells expressing WT-SLCO2A1 exhibited time- and dose-dependent uptake of PGE2, while the mutant did not show any uptake activity. Residue L563 is very close to the putative substrate-binding site in SLCO2A1, R561 in helix 11. However, in a molecular model of SLCO2A1, the side chain of L563 projected outside of helix 11, indicating that L563 is likely not directly involved in substrate binding. Instead, the substitution of Pro may twist the helix and impair the transporter function. In summary, we identified a novel pathogenic variant of SLCO2A1 that caused loss-of-function and induced CEAS.
 ...
PMID:A novel mutation in the SLCO2A1 gene, encoding a prostaglandin transporter, induces chronic enteropathy. 3316 38