{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T19:57:10Z","timestamp":1779134230321,"version":"3.51.4"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T00:00:00Z","timestamp":1652227200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,5,11]],"date-time":"2022-05-11T00:00:00Z","timestamp":1652227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Jonty Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Mutations or polymorphisms of genes that are associated with inflammasome functions are known to predispose individuals to Crohn\u2019s disease and likely affect clinical presentations and responses to therapeutic agents in patients with Crohn\u2019s disease. The presence of additional gene mutations\/polymorphisms that can modify immune responses may further affect clinical features, making diagnosis and management of Crohn\u2019s disease even more challenging. Whole-exome sequencing is expected to be instrumental in understanding atypical presentations of Crohn\u2019s disease and the selection of therapeutic measures, especially when multiple gene mutations\/polymorphisms affect patients with Crohn\u2019s disease.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case summary<\/jats:title>\n                <jats:p>We report the case of a non-Hispanic Caucasian female patient with Crohn\u2019s disease who was initially diagnosed with pediatric acute-onset neuropsychiatric syndrome with fluctuating anxiety symptoms at 9 years of age. This patient was initially managed with pulse oral corticosteroid treatment and then intravenous immunoglobulin due to her immunoglobulin G1 deficiency. At 15 years of age, she was diagnosed with Crohn\u2019s disease, following onset of acute abdomen. Treatment with oral corticosteroid and then tumor necrosis factor-\u03b1 blockers (adalimumab and infliximab) led to remission of Crohn\u2019s disease. However, she continued to suffer from chronic abdominal pain, persistent headache, general fatigue, and joint ache involving multiple joints. Extensive gastrointestinal workup was unrevealing, but whole-exome sequencing identified two autosomal dominant gene variants: <jats:italic>NLRP12<\/jats:italic> (loss of function) and <jats:italic>IRF2BP2<\/jats:italic> (gain of function). Based on whole-exome sequencing findings, infliximab was discontinued and anakinra, an interleukin-1\u03b2 blocker, was started, rendering marked improvement of her clinical symptoms. However, Crohn\u2019s disease lesions recurred following <jats:italic>Yersinia<\/jats:italic> enterocolitis. The patient was successfully treated with a blocker of interleukin-12p40 (ustekinumab), and anakinra was discontinued following remission of her Crohn\u2019s disease lesions.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Loss-of-function mutation of <jats:italic>NRLRP12<\/jats:italic> gene augments production of interleukin-1\u03b2 and tumor necrosis factor-\u03b1, while gain-of-function mutation of <jats:italic>IRF2BP2<\/jats:italic> impairs cytokine production and B cell differentiation. We propose that the presence of these two autosomal dominant variants caused an atypical clinical presentation of Crohn\u2019s disease.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13256-022-03404-9","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T23:02:38Z","timestamp":1652223758000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Whole-exome sequencing in a subject with fluctuating neuropsychiatric symptoms, immunoglobulin G1 deficiency, and subsequent development of Crohn\u2019s disease: a case report"],"prefix":"10.1186","volume":"16","author":[{"given":"Harumi","family":"Jyonouchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Geng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,5,11]]},"reference":[{"issue":"1","key":"3404_CR1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.cmet.2017.06.018","volume":"26","author":"T Prochnicki","year":"2017","unstructured":"Prochnicki T, Latz E. 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A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"There are no financial or nonfinancial competing interests to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"187"}}