{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:24:53Z","timestamp":1773278693591,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T00:00:00Z","timestamp":1624924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070027"],"award-info":[{"award-number":["82070027"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Interferon\u2010induced with helicase C domain 1 (IFIH1) is a cytosolic sensor of dsRNA that induces an anti\u2010viral Type I interferon (IFN) state. A gain\u2010of\u2010function mutation in\n                    <jats:italic>IFIH1<\/jats:italic>\n                    can cause increased Type I IFN activity and is clinically associated with Aicardi\u2013Gouti\u00e8res syndrome (AGS). AGS is a multisystem disease, characterized as an early\u2010onset progressive encephalopathy with basal ganglia calcification and systemic lupus erythematosus\u2010like features. Gastrointestinal manifestation is rare in AGS patients. We described a 10\u2010year\u2010old female patient with a heterozygous\n                    <jats:italic>IFIH1<\/jats:italic>\n                    gene mutation who presented with gastrointestinal colitis, cystitis and very severe diarrhea as initial major manifestations of AGS. Proteinuria with high titer of antinuclear antibody and anti\u2010double\u2010stranded DNA was found in this patient. She also had growth retardation and a history of seizures (about two episodes each year) but without attacks until 7\u2009years old. Serum cytokines detected by flow cytometry indicated extremely high level of interleukin 6 (1970.1\u00a0pg\/ml) and IFN\u2010\u03b1 (204.1\u00a0pg\/ml). A contrast\u2010enhanced CT scan of the whole abdomen and an intestinal hydro\u2010MRI indicated that the walls of her stomach, small bowel, colon, and bladder were in various degrees of edema and thickened states. Whole exome sequencing analysis indicated that she harbors an\n                    <jats:italic>IFIH1<\/jats:italic>\n                    heterozygous mutation (c.2336G\u2009&gt;\u2009A (p.R779H)) in both blood and intestinal samples. Abundant inflammatory cells infiltration into the intestinal epithelium was observed by immunohistochemical staining. Positive staining of caspase 4 and caspase 5 suggested that the signaling pathway of pyroptosis was involved in the mechanism of intestinal inflammation in AGS. Diarrhea was significantly improved after steroids and intravenous immunoglobulin treatments. Gastrointestinal colitis and cystitis can be rare manifestations of AGS with\n                    <jats:italic>IFIH1<\/jats:italic>\n                    mutation. Caspase and its related inflammasome pathway may involve in the pathogenesis of AGS.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.62397","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T22:54:52Z","timestamp":1625093692000},"page":"3146-3152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Severe diarrhea in a 10\u2010year\u2010old girl with\n                    <scp>Aicardi\u2013Gouti\u00e8res<\/scp>\n                    syndrome due to\n                    <scp>\n                      <i>IFIH1<\/i>\n                    <\/scp>\n                    gene mutation"],"prefix":"10.1002","volume":"185","author":[{"given":"Meiping","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Rheumatology Immunology and Allergy Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pathology Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3182-4235","authenticated-orcid":false,"given":"Qi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Immunology and Allergy Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohui","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Radiology Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixia","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Immunology and Allergy Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2018.09.004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410150109"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2017.09.002"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2019.04.003"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.58"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.14073"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36887"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3850"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000013893"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8050750"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1093526619837797"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000001792"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12287"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2017.05.005"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37577"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.06.007"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2933"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23975"},{"key":"e_1_2_9_20_1","first-page":"603","article-title":"Gasdermins in apoptosis: New players in an old game","volume":"92","author":"Rogers C.","year":"2019","journal-title":"Yale Journal of Biology and Medicine"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.036"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/nxg.0000000000000384"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00737-3"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39110"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00985"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62397","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62397","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62397","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T10:54:29Z","timestamp":1773226469000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62397"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,29]]},"references-count":24,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1002\/ajmg.a.62397"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62397","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,29]]},"assertion":[{"value":"2021-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}