{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:47:30Z","timestamp":1782150450939,"version":"3.54.5"},"reference-count":13,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Pseudo-TORCH syndrome type 2 is a rare autosomal recessive disorder caused by biallelic variants in the\n                      <jats:italic toggle=\"yes\">USP18<\/jats:italic>\n                      gene. Clinically, affected individuals exhibit multisystem involvement, including intracranial calcification (ICC) and haemorrhage, seizures, hepatosplenomegaly, and thrombocytopenia. To date, only 11 cases have been reported in the literature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case report<\/jats:title>\n                    <jats:p>We report a case of an Indian girl child born to consanguineous parents, presenting with recurrent febrile encephalopathy, developmental delay, microcephaly, tone abnormalities, organomegaly, thrombocytopenia, and ICCs. A similar clinical history was noted in the elder sibling who succumbed to the same illness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Exome sequencing revealed a novel homozygous missense variant, c.358C&gt;T (p.Pro120Ser), in exon four of the\n                      <jats:italic toggle=\"yes\">USP18<\/jats:italic>\n                      gene. Sanger sequencing of the asymptomatic parents confirmed heterozygosity of this variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      To our knowledge, this is the first reported case of\n                      <jats:italic toggle=\"yes\">USP18<\/jats:italic>\n                      -related disease presenting with recurrent febrile encephalopathy. Further studies are required to understand better the variable presentations associated with the disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/mcd.0000000000000538","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T02:03:29Z","timestamp":1762481009000},"page":"7-14","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["USP18 gene mutation associated with recurrent encephalopathy, intracranial calcification, and microcephaly: case report, long-term follow-up, and literature review"],"prefix":"10.1097","volume":"35","author":[{"given":"Vykuntaraju K.","family":"Gowda","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varunvenkat M.","family":"Srinivasan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Postgraduate Institute of Child Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Archana","family":"Varghese","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uddhava V.","family":"Kinhal","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himani","family":"Pandey","sequence":"additional","affiliation":[{"name":"Departartment of Molecular Genetics, Redcliffe Labs, Noida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devi","family":"Lal","sequence":"additional","affiliation":[{"name":"Department of Zoology, Ramjas College, University of Delhi, Delhi, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"R1-20260622","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1056\/NEJMoa1905633","article-title":"JAK inhibitor therapy in a child with inherited USP18 deficiency.","volume":"382","author":"Alsohime","year":"2020","journal-title":"N Engl J Med"},{"key":"R2-20260622","doi-asserted-by":"crossref","first-page":"W344","DOI":"10.1093\/nar\/gkw408","article-title":"ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules.","volume":"44","author":"Ashkenazy","year":"2016","journal-title":"Nucleic Acids Res"},{"key":"R3-20260622","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/ajmg.a.20138","article-title":"Two brothers with findings resembling congenital intrauterine infection-like syndrome (pseudo-TORCH syndrome).","volume":"120A","author":"Knoblauch","year":"2003","journal-title":"Am J Med Genet A"},{"key":"R4-20260622","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1111\/dmcn.12359","article-title":"Intracranial calcification in childhood: a review of aetiologies and recognizable phenotypes.","volume":"56","author":"Livingston","year":"2014","journal-title":"Dev Med Child Neurol"},{"key":"R5-20260622","doi-asserted-by":"crossref","first-page":"9976","DOI":"10.1074\/jbc.M109078200","article-title":"UBP43 (USP18) specifically removes ISG15 from conjugated proteins.","volume":"277","author":"Malakhov","year":"2002","journal-title":"J Biol Chem"},{"key":"R6-20260622","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1084\/jem.20211273","article-title":"A partial form of inherited human USP18 deficiency underlies infection and inflammation.","volume":"219","author":"Martin-Fernandez","year":"2022","journal-title":"J Exp Med"},{"key":"R13-20260622","doi-asserted-by":"crossref","first-page":"3555532","DOI":"10.1155\/2022\/3555532","article-title":"A case report and literature review of pseudo\u2010TORCH syndrome type 2 (PTORCH2).","volume":"2022","author":"Misk","year":"2022","journal-title":"Case Rep Pediatr"},{"key":"R7-20260622","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1084\/jem.20151529","article-title":"Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome.","volume":"213","author":"Meuwissen","year":"2016","journal-title":"J Exp Med"},{"key":"R8-20260622","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"R9-20260622","first-page":"135","article-title":"A novel familial case report of genetic syndrome mimicking congenital TORCH infections; pseudo-TORCH syndrome 2.","volume":"23","author":"Sehrish","year":"2022","journal-title":"J Reprod Infertil"},{"key":"R10-20260622","doi-asserted-by":"crossref","first-page":"e63899","DOI":"10.1002\/ajmg.a.63899","article-title":"Expanding the phenotype of NRROS-related SENEBAC syndrome.","volume":"197","author":"Srinivasan","year":"2024","journal-title":"Am J Med Genet A"},{"key":"R11-20260622","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: homology modelling of protein structures and complexes.","volume":"46","author":"Waterhouse","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"R12-20260622","doi-asserted-by":"crossref","first-page":"W122","DOI":"10.1093\/nar\/gkad472","article-title":"DDMut: predicting effects of mutations on protein stability using deep learning.","volume":"51","author":"Zhou","year":"2023","journal-title":"Nucleic Acids Res"}],"container-title":["Clinical Dysmorphology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/MCD.0000000000000538","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T17:00:23Z","timestamp":1782147623000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/MCD.0000000000000538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":13,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1097\/mcd.0000000000000538","relation":{},"ISSN":["0962-8827","1473-5717"],"issn-type":[{"value":"0962-8827","type":"print"},{"value":"1473-5717","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,15]]},"assertion":[{"value":"2025-04-28","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-27","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}