{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T12:56:59Z","timestamp":1773061019079,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Immunogenetics"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Familial cold autoinflammatory syndrome 2 is a rare autoinflammatory disorder caused by mutations in the\n                    <jats:italic>NLRP12<\/jats:italic>\n                    gene, characterized by recurrent fever, arthralgia and rash triggered by cold exposure. This case report presents a 9\u2010year\u2010old boy with intellectual disability, microcephaly and skin lesions, where genetic testing revealed heterozygous pathogenic variants in both\n                    <jats:italic>KIF11<\/jats:italic>\n                    (NM_004523.4:c.2304_2305del) and\n                    <jats:italic>NLRP12<\/jats:italic>\n                    (NM_144687.4:c.770del) genes. While the\n                    <jats:italic>KIF11<\/jats:italic>\n                    variant has been previously documented, the\n                    <jats:italic>NLRP12<\/jats:italic>\n                    variant is novel and classified as likely pathogenic. This study also includes a systematic review analysing 28 studies and 100 patients with\n                    <jats:italic>NLRP12<\/jats:italic>\n                    mutations, revealing a phenotypic spectrum ranging from classic symptoms like fever and rash to rarer features such as hypogonadism, hypothyroidism and neurological abnormalities. A significant concentration of variants was noted in Exon 3 of\n                    <jats:italic>NLRP12<\/jats:italic>\n                    , but no clear genotype\u2013phenotype correlation was established. These findings underscore the utility of next\u2010generation sequencing in diagnosing rare genetic conditions, particularly in patients presenting with seemingly minor symptoms. The coexistence of mutations in\n                    <jats:italic>KIF11<\/jats:italic>\n                    and\n                    <jats:italic>NLRP12<\/jats:italic>\n                    highlights potential interactions between distinct genetic pathways, emphasizing the need for further research. Including\n                    <jats:italic>NLRP12<\/jats:italic>\n                    in diagnostic panels and updating databases like the Human Phenotype Ontology are crucial for improving diagnosis, understanding phenotypic diversity and optimizing patient management.\n                  <\/jats:p>","DOI":"10.1111\/iji.70028","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T05:25:33Z","timestamp":1763616333000},"page":"73-82","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Variant in the\n                    <i>NLRP12<\/i>\n                    Gene: Insights From a Case Report and Systematic Review"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3618-5396","authenticated-orcid":false,"given":"Abdelhamid","family":"Bouramtane","sequence":"first","affiliation":[{"name":"Medical Genetics &amp; Oncogenetics Laboratory Hassan II University Hospital Center  Fez Morocco"},{"name":"Faculty of Medicine Pharmacy and Dentistry Sidi Mohamed Ben Abdellah University  Fez Morocco"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5312-8612","authenticated-orcid":false,"given":"Badreddine","family":"Elmakhzen","sequence":"additional","affiliation":[{"name":"Medical Genetics &amp; 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