{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:06:20Z","timestamp":1789506380965,"version":"build-2803163510"},"reference-count":16,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009053","name":"The Wellcome Trust DBT India Alliance","doi-asserted-by":"publisher","award":["IA\/CPHE\/20\/1\/505226"],"award-info":[{"award-number":["IA\/CPHE\/20\/1\/505226"]}],"id":[{"id":"10.13039\/501100009053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,3]]},"abstract":"Abstract<\/jats:title>\n \n The evolutionarily conserved mevalonate pathway plays an important role in the synthesis of cholesterol and isoprenoid compounds. Mevalonate kinase (\n MVK<\/jats:italic>\n ) and phosphomevalonate kinase (\n PMVK<\/jats:italic>\n ) enzymes regulate key rate\u2010limiting steps in this pathway by sequentially phosphorylating mevalonic acid to yield downstream metabolites that regulate protein prenylation and cell signaling. Biallelic pathogenic variants in\n MVK<\/jats:italic>\n cause a spectrum of rare autoinflammatory disorders that encompass milder forms of hyper\u2010IgD syndrome (HIDS) at one end and the more severe mevalonic aciduria on the other. In contrast, pathogenic variants reported in\n PMVK<\/jats:italic>\n are heterozygous and associated with porokeratosis, a skin disorder with no systemic manifestations. Recently, biallelic variants in\n PMVK<\/jats:italic>\n were reported as a cause for an autoinflammatory disorder for the first time in two unrelated patients. In this study, we describe a child with recurrent arthritis and a HIDS\u2010like phenotype harboring a novel homozygous variant c.398 C>T (p.Ala133Val) in\n PMVK.<\/jats:italic>\n Mononuclear cells isolated from the patient showed significantly elevated production of interleukin 1\u03b2, a key cytokine that shapes the inflammatory response in HIDS. Protein modeling studies suggested potential defects in PMVK enzyme activity. These results posit a further expanding of the genotypic spectrum of autoinflammatory disease to include biallelic\n PMVK<\/jats:italic>\n variants.\n <\/jats:p>","DOI":"10.1111\/cge.14451","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T01:49:16Z","timestamp":1701222556000},"page":"302-307","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A novel homozygous variant in\n PMVK<\/i>\n is associated with enhanced\n IL1\u03b2<\/scp>\n secretion and a\n hyper\u2010IgD<\/scp>\n syndrome\u2010like phenotype"],"prefix":"10.1111","volume":"105","author":[{"given":"Amit","family":"Jairaman","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaishnavi Ashok","family":"Badiger","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spoorthy","family":"Raj","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Amrita Institute of Medical Sciences Kochi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik Vijay","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education Manipal India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suma","family":"Balan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Amrita Institute of Medical Sciences Kochi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1627-3252","authenticated-orcid":false,"given":"Dhanya Lakshmi","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kasturba Medical College, Manipal Academy of Higher Education Manipal India"},{"name":"DBT\u2010Wellcome Trust India Alliance Early Career Clinical and Public Health Research Fellow Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2021.05.002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2012.09.011"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/9691"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20361"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2409"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.06322"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep24226"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.06.013"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2022.105490"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.22151"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.12.3586.bloodjournal85123586"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3457"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3487"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1358-4"}],"container-title":["Clinical 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