{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:11:31Z","timestamp":1790223091242,"version":"4.1.0"},"reference-count":51,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Gut"],"accepted":{"date-parts":[[2012,11,21]]},"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cryptogenic multifocal ulcerating stenosing enteritis (CMUSE) is an extremely rare, but devastating, disease of unknown aetiology. We investigated the genetic basis of this autosomal recessive condition in a pair of affected siblings who have 40-year histories of catastrophic gastrointestinal and extraintestinal disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Genome-wide single-nucleotide polymorphism homozygosity mapping in the two affected family members combined with whole-exome sequencing of one affected sibling. This was followed by confirmatory Sanger sequencing of the likely disease-causing sequence variant and functional studies in affected and unaffected family members.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Insertion\/deletion variation analysis revealed the presence of a homozygous 4 bp deletion (g.155574_77delGTAA) in the\n                      <jats:italic>PLA2G4A<\/jats:italic>\n                      gene, located in the splice donor site directly after exon 17 (the penultimate exon) of the gene in both affected siblings. This introduces a frameshift of 10 amino acids before a premature stop codon (p.V707fsX10), which is predicted to result in the loss of 43 amino acids (residues 707\u2013749) at the C-terminus of cytosolic phospholipase A2-\u03b1 (cPLA\n                      <jats:sub>2<\/jats:sub>\n                      \u03b1). cPLA\n                      <jats:sub>2<\/jats:sub>\n                      \u03b1 protein expression was undetectable in the gut of both siblings, with platelet aggregation and thromboxane A\n                      <jats:sub>2<\/jats:sub>\n                      production, as functional assays for cPLA\n                      <jats:sub>2<\/jats:sub>\n                      \u03b1 activity, grossly impaired.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We have identified mutations in\n                      <jats:italic>PLA2G4A<\/jats:italic>\n                      as a cause of CMUSE in two affected siblings. Further studies are needed to determine if mutations in this gene are also responsible for disease of a similar phenotype in other cases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2012-303581","type":"journal-article","created":{"date-parts":[[2012,12,25]],"date-time":"2012-12-25T20:26:18Z","timestamp":1356467178000},"page":"96-104","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":63,"title":["Cryptogenic multifocal ulcerating stenosing enteritis associated with homozygous deletion mutations in cytosolic phospholipase A2-\u03b1"],"prefix":"10.1136","volume":"63","author":[{"given":"Matthew A","family":"Brooke","sequence":"first","affiliation":[{"name":"Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary J","family":"Longhurst","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology, Barts Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Plagnol","sequence":"additional","affiliation":[{"name":"Department of Genetics, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas S","family":"Kirkby","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"},{"name":"National Heart and Lung Institute, Imperial College, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A","family":"Mitchell","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"R\u00fcschendorf","sequence":"additional","affiliation":[{"name":"Max-Delbr\u00fcck-Center for Molecular Medicine, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D","family":"Warner","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P","family":"Kelsell","sequence":"additional","affiliation":[{"name":"Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas T","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2012,12,25]]},"reference":[{"key":"2025120520260070000_63.1.96.1","doi-asserted-by":"publisher","DOI":"10.1038\/83713"},{"key":"2025120520260070000_63.1.96.2","doi-asserted-by":"publisher","DOI":"10.1007\/s002510100358"},{"key":"2025120520260070000_63.1.96.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907206"},{"key":"2025120520260070000_63.1.96.4","doi-asserted-by":"crossref","unstructured":"Moran CJ Walters TD Guo CH . 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