{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T02:19:30Z","timestamp":1793067570109,"version":"4.5.0"},"reference-count":47,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"accepted":{"date-parts":[[2012,4,1]]},"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Multiple genes have been implicated by association studies in altering inflammatory bowel disease (IBD) predisposition. Paediatric patients often manifest more extensive disease and a particularly severe disease course. It is likely that genetic predisposition plays a more substantial role in this group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify the spectrum of rare and novel variation in known IBD susceptibility genes using exome sequencing analysis in eight individual cases of childhood onset severe disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>DNA samples from the eight patients underwent targeted exome capture and sequencing. Data were processed through an analytical pipeline to align sequence reads, conduct quality checks, and identify and annotate variants where patient sequence differed from the reference sequence. For each patient, the entire complement of rare variation within strongly associated candidate genes was catalogued.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across the panel of 169 known IBD susceptibility genes, approximately 300 variants in 104 genes were found. Excluding splicing and\n                      <jats:italic>HLA<\/jats:italic>\n                      -class variants, 58 variants across 39 of these genes were classified as rare, with an alternative allele frequency of &lt;5%, of which 17 were novel. Only two patients with early onset Crohn's disease exhibited rare deleterious variations within\n                      <jats:italic>NOD2<\/jats:italic>\n                      : the previously described R702W variant was the sole\n                      <jats:italic>NOD2<\/jats:italic>\n                      variant in one patient, while the second patient also carried the L1007 frameshift insertion. Both patients harboured other potentially damaging mutations in the\n                      <jats:italic>GSDMB<\/jats:italic>\n                      ,\n                      <jats:italic>ERAP2<\/jats:italic>\n                      and\n                      <jats:italic>SEC16A<\/jats:italic>\n                      genes. The two patients severely affected with ulcerative colitis exhibited a distinct profile: both carried potentially detrimental variation in the\n                      <jats:italic>BACH2<\/jats:italic>\n                      and\n                      <jats:italic>IL10<\/jats:italic>\n                      genes not seen in other patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>For each of the eight individuals studied, all non-synonymous, truncating and frameshift mutations across all known IBD genes were identified. A unique profile of rare and potentially damaging variants was evident for each patient with this complex disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/gutjnl-2011-301833","type":"journal-article","created":{"date-parts":[[2012,4,28]],"date-time":"2012-04-28T20:55:11Z","timestamp":1335646511000},"page":"977-984","source":"Crossref","is-referenced-by-count":108,"title":["Next generation exome sequencing of paediatric inflammatory bowel disease patients identifies rare and novel variants in candidate genes"],"prefix":"10.1136","volume":"62","author":[{"given":"Katja","family":"Christodoulou","sequence":"first","affiliation":[{"name":"Genetic Epidemiology and Genomic Informatics Group, Human Genetics & Genomic Medicine, Faculty of Medicine, University of Southampton, Duthie Building (Mailpoint 808), University Hospital Southampton NHS Foundation Trust, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E","family":"Wiskin","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Unit (Nutrition, Diet & Lifestyle), University Hospital Southampton NHS Foundation Trust, Mailpoint 218, Southampton General Hospital, Tremona Road, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Gibson","sequence":"additional","affiliation":[{"name":"Genetic Epidemiology and Genomic Informatics Group, Human Genetics & Genomic Medicine, Faculty of Medicine, University of Southampton, Duthie Building (Mailpoint 808), University Hospital Southampton NHS Foundation Trust, Southampton, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Tapper","sequence":"additional","affiliation":[{"name":"Genetic Epidemiology and Genomic Informatics Group, Human Genetics & Genomic Medicine, Faculty of Medicine, University of Southampton, Duthie Building (Mailpoint 808), University Hospital Southampton NHS Foundation Trust, 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