{"id":46353,"date":"2025-10-21T09:59:30","date_gmt":"2025-10-21T07:59:30","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/10\/21\/identification-and-functional-validation-of-novel-pathogenic-variants-in-primary-immunodeficiencies-valuearvinden-vr-geeta-madathil-govindaraj-aditya-ramdas-iyer-sangita-paul-athuly\/"},"modified":"2025-10-21T09:59:30","modified_gmt":"2025-10-21T07:59:30","slug":"identification-and-functional-validation-of-novel-pathogenic-variants-in-primary-immunodeficiencies-valuearvinden-vr-geeta-madathil-govindaraj-aditya-ramdas-iyer-sangita-paul-athuly","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/10\/21\/identification-and-functional-validation-of-novel-pathogenic-variants-in-primary-immunodeficiencies-valuearvinden-vr-geeta-madathil-govindaraj-aditya-ramdas-iyer-sangita-paul-athuly\/","title":{"rendered":"Identification and Functional Validation of Novel Pathogenic Variants in Primary Immunodeficiencies. [[{&#8220;value&#8221;:&#8221;Arvinden VR, \nGeeta Madathil Govindaraj, \nAditya Ramdas Iyer, \nSangita Paul, \nAthulya Edavazhippurath, \nAbhinav Jain, \nPragya Gupta, \nGauspasha Yusuf Deshmukh, \nShivani Singh, \nVinodh Saravanakumar, \nJuhi Bhardwaj, \nSrishti Sharma, \nTancia P. Benny, \nPriya Saravanan, \nRahul C. Bhoyar, \nMohamed Imran, \nVigneshwar Senthivel, \nMohit Kumar Divakar, \nHarie Vignesh, \nBani Jolly, \nAparna Dalvi, \nUmair Ahmed Bargir, \nManisha Madkaikar, \nBinukumar BK, \nSridhar Sivasubbu, \nSivaprakash Ramalingam, \nVinod Scaria&#8221;}]]"},"content":{"rendered":"<p><img decoding=\"async\" src=\"https:\/\/onlinelibrary.wiley.com\/cms\/asset\/d4c58dd3-5f88-4d93-8f78-199eecba3225\/eji70057-gra-0001-m.png\" alt=\"Identification and Functional Validation of Novel Pathogenic Variants in Primary Immunodeficiencies\" \/><\/p>\n<p>Primary immunodeficiency is a monogenic disorder that affects proper immune functioning. Diagnostic yield of these inherited diseases are burdened by the presence of variants of unknown significance. In this study we functionally validated novel variants associated with immunodeficiency to ascertain its pathogenicity.<\/p>\n<p><\/p>\n<h2>ABSTRACT<\/h2>\n<p>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-generation sequencing (NGS) technology enables the identification of molecular defects, improving the diagnosis of PIDs. Functional validation of genetic variants identified through PID-related gene screenings is crucial for determining their clinical significance. In this study, we identified five novel variants in PID-related genes in six families using whole-exome sequencing. These variants include <i>FCHO1<\/i> (E44K), <i>NCF2<\/i> (A206P), <i>NCF2<\/i> (c.174 + 1G &gt; A), <i>STAT1<\/i> (L199F), and a copy number deletion in <i>LRBA<\/i> (exon 9\u201317). Functional validation was performed for four of these variants: <i>STAT1<\/i> (L199F) using pSTAT1 assay, <i>NCF2<\/i> (A206P and c.174 + 1G &gt; A) by DHR assay, and FCHO1 (E44K) using CRISPR-mediated genome editing. Overall, the present study expands the knowledge of previously unreported variants in primary immunodeficiency.<\/p>","protected":false},"excerpt":{"rendered":"<p>Primary immunodeficiency is a monogenic disorder that affects proper immune functioning. Diagnostic yield of these inherited diseases are burdened by the presence of variants of unknown significance. In this study we functionally validated novel variants associated with immunodeficiency to ascertain its pathogenicity. ABSTRACT Primary immunodeficiency diseases (PIDs) are inherited disorders caused by genetic defects affecting &#8230; <a title=\"Identification and Functional Validation of Novel Pathogenic Variants in Primary Immunodeficiencies. [[{&#8220;value&#8221;:&#8221;Arvinden VR, \nGeeta Madathil Govindaraj, \nAditya Ramdas Iyer, \nSangita Paul, \nAthulya Edavazhippurath, \nAbhinav Jain, \nPragya Gupta, \nGauspasha Yusuf Deshmukh, \nShivani Singh, \nVinodh Saravanakumar, \nJuhi Bhardwaj, \nSrishti Sharma, \nTancia P. Benny, \nPriya Saravanan, \nRahul C. Bhoyar, \nMohamed Imran, \nVigneshwar Senthivel, \nMohit Kumar Divakar, \nHarie Vignesh, \nBani Jolly, \nAparna Dalvi, \nUmair Ahmed Bargir, \nManisha Madkaikar, \nBinukumar BK, \nSridhar Sivasubbu, \nSivaprakash Ramalingam, \nVinod Scaria&#8221;}]]\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/10\/21\/identification-and-functional-validation-of-novel-pathogenic-variants-in-primary-immunodeficiencies-valuearvinden-vr-geeta-madathil-govindaraj-aditya-ramdas-iyer-sangita-paul-athuly\/\" aria-label=\"Read more about Identification and Functional Validation of Novel Pathogenic Variants in Primary Immunodeficiencies. [[{&#8220;value&#8221;:&#8221;Arvinden VR, \nGeeta Madathil Govindaraj, \nAditya Ramdas Iyer, \nSangita Paul, \nAthulya Edavazhippurath, \nAbhinav Jain, \nPragya Gupta, \nGauspasha Yusuf Deshmukh, \nShivani Singh, \nVinodh Saravanakumar, \nJuhi Bhardwaj, \nSrishti Sharma, \nTancia P. Benny, \nPriya Saravanan, \nRahul C. Bhoyar, \nMohamed Imran, \nVigneshwar Senthivel, \nMohit Kumar Divakar, \nHarie Vignesh, \nBani Jolly, \nAparna Dalvi, \nUmair Ahmed Bargir, \nManisha Madkaikar, \nBinukumar BK, \nSridhar Sivasubbu, \nSivaprakash Ramalingam, \nVinod Scaria&#8221;}]]\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[112,42],"tags":[],"class_list":["post-46353","post","type-post","status-publish","format-standard","hentry","category-european-journal-of-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/46353","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=46353"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/46353\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=46353"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=46353"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=46353"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}