{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T06:50:08Z","timestamp":1761547808296,"version":"build-2065373602"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Primary immunodeficiency diseases (PIDs) are inherited disorders caused by genetic defects affecting immune function, leading to recurrent infections, autoimmunity, and malignancies. Many PIDs remain genetically uncharacterized, largely due to rare variants with unclear pathogenicity, which complicates the process of establishing an accurate diagnosis. Next\u2010generation sequencing (NGS) technology enables the identification of molecular defects, improving the diagnosis of PIDs. Functional validation of genetic variants identified through PID\u2010related gene screenings is crucial for determining their clinical significance. In this study, we identified five novel variants in PID\u2010related genes in six families using whole\u2010exome sequencing. These variants include\n                    <jats:italic>FCHO1<\/jats:italic>\n                    (E44K),\n                    <jats:italic>NCF2<\/jats:italic>\n                    (A206P),\n                    <jats:italic>NCF2<\/jats:italic>\n                    (c.174 + 1G &gt; A),\n                    <jats:italic>STAT1<\/jats:italic>\n                    (L199F), and a copy number deletion in\n                    <jats:italic>LRBA<\/jats:italic>\n                    (exon 9\u201317). Functional validation was performed for four of these variants:\n                    <jats:italic>STAT1<\/jats:italic>\n                    (L199F) using pSTAT1 assay,\n                    <jats:italic>NCF2<\/jats:italic>\n                    (A206P and c.174 + 1G &gt; A) by DHR assay, and FCHO1 (E44K) using CRISPR\u2010mediated genome editing. Overall, the present study expands the knowledge of previously unreported variants in primary immunodeficiency.\n                  <\/jats:p>","DOI":"10.1002\/eji.70057","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:19:37Z","timestamp":1761020377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Functional Validation of Novel Pathogenic Variants in Primary Immunodeficiencies"],"prefix":"10.1002","volume":"55","author":[{"given":"Arvinden","family":"VR","sequence":"first","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geeta Madathil","family":"Govindaraj","sequence":"additional","affiliation":[{"name":"Department of Pediatrics FPID Regional Diagnostic Centre Government Medical College Kozhikode  Kozhikode India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aditya Ramdas","family":"Iyer","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad India"},{"name":"Department of Biological Sciences and Bioengineering and Mehta Family Centre for Engineering in Medicine Indian Institute of Technology Kanpur  Kanpur India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangita","family":"Paul","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Athulya","family":"Edavazhippurath","sequence":"additional","affiliation":[{"name":"Department of Pediatrics FPID Regional Diagnostic Centre Government Medical College Kozhikode  Kozhikode India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhinav","family":"Jain","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pragya","family":"Gupta","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gauspasha Yusuf","family":"Deshmukh","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shivani","family":"Singh","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinodh","family":"Saravanakumar","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juhi","family":"Bhardwaj","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad 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C.","family":"Bhoyar","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Vishwanath Cancer Care Foundation  Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Imran","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vigneshwar","family":"Senthivel","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohit Kumar","family":"Divakar","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harie","family":"Vignesh","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bani","family":"Jolly","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aparna","family":"Dalvi","sequence":"additional","affiliation":[{"name":"Department of Pediatric Immunology ICMR National Institute of Immunohematology  Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umair Ahmed","family":"Bargir","sequence":"additional","affiliation":[{"name":"Department of Pediatric Immunology ICMR National Institute of Immunohematology  Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manisha","family":"Madkaikar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Immunology ICMR National Institute of Immunohematology  Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Binukumar","family":"BK","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and Integrative Biology (CSIR\u2010IGIB)  Delhi India"},{"name":"Academy of Scientific and Innovative Research (AcSIR) CSIR\u2010HRDC Campus  Ghaziabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sridhar","family":"Sivasubbu","sequence":"additional","affiliation":[{"name":"CSIR Institute of Genomics and 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CSIR\u2010HRDC Campus  Ghaziabad India"},{"name":"Vishwanath Cancer Care Foundation  Mumbai India"},{"name":"Hospital &amp; Research Centre Dr. D. Y. Patil Medical College  Pune India"},{"name":"Gangwal School Medical Science and Technology Indian Institute of Technology  Kanpur India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01289-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010022\u201001352\u2010z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2020.1801422"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.906540"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13223-022-00662-6"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.02.014"},{"key":"e_1_2_10_9_1","first-page":"1","article-title":"Human FCHO1 Deficiency Reveals Role for Clathrin\u2010Mediated Endocytosis in Development and Function of T Cells","volume":"11","author":"\u0141yszkiewicz M.","year":"2020","journal-title":"Nature Communications"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bty304"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.7.2505.419k10_2505_2514"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.015"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.24051"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00847-x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110958"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-679902"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06045-0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.09.025"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010007\u20109123\u2010x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2018.77383"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2018.12.022"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-015-0144-2"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010017\u20100636\u20102"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875\u2010016\u20100299\u20109"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01276-8"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2011.61"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201018040\u2010y"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.129684.111"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01449-0"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1271\/bbb.60720"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0308873"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.70057","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T06:46:03Z","timestamp":1761547563000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.70057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/eji.70057"],"URL":"https:\/\/doi.org\/10.1002\/eji.70057","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"type":"print","value":"0014-2980"},{"type":"electronic","value":"1521-4141"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2024-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70057"}}