{"id":49361,"date":"2025-11-22T12:00:00","date_gmt":"2025-11-22T11:00:00","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/11\/22\/whole-genome-sequencing-in-25-families-with-suspected-inborn-errors-of-immunity-diagnostic-yield-and-clinical-relevance-of-genome-wide-analysis\/"},"modified":"2025-11-22T12:00:00","modified_gmt":"2025-11-22T11:00:00","slug":"whole-genome-sequencing-in-25-families-with-suspected-inborn-errors-of-immunity-diagnostic-yield-and-clinical-relevance-of-genome-wide-analysis","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/11\/22\/whole-genome-sequencing-in-25-families-with-suspected-inborn-errors-of-immunity-diagnostic-yield-and-clinical-relevance-of-genome-wide-analysis\/","title":{"rendered":"Whole Genome Sequencing in 25 Families with Suspected Inborn Errors of Immunity: Diagnostic Yield and Clinical Relevance of Genome-wide Analysis"},"content":{"rendered":"
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J Clin Immunol<\/b>. 2025 Nov 23. doi: 10.1007\/s10875-025-01947-2. Online ahead of print.<\/p>\n

ABSTRACT<\/b><\/p>\n

INTRODUCTION: Inborn errors of immunity (IEIs) constitute a diverse group of more than 500 disorders resulting from pathogenic variants in over 500 causative genes, with most being monogenic diseases. The use of exome sequencing based on next-generation sequencing technologies has significantly advanced the discovery of causative variants underlying IEIs and has achieved diagnostic yields of up to 40%. Despite these advances, a substantial proportion of patients still remain genetically undiagnosed due to limitations in detecting deep intronic or structural variants. Accordingly, we applied whole-genome sequencing to a cohort of patients suspected of IEIs in order to evaluate its diagnostic yield and capacity to identify novel structural genomic alterations.<\/p>\n

METHODS: We analyzed data from 25 probands presenting with suspected IEIs based on clinical features, who were enrolled through the National Bio-Big Data Program’s whole genome sequencing (WGS) project at Samsung Medical Center, spanning July 2020 to February 2022. The study utilized a stepwise analytical protocol involving initial candidate gene panel analysis for detecting small variants, subsequent investigation of structural variants, and then a genotype-driven approach utilizing in-house bioinformatics pipelines. All identified variants were assessed for pathogenicity in accordance with the 2015 ACMG\/AMP guidelines for the interpretation of sequence variants.<\/p>\n

RESULTS: Causative variants were detected in 10 (40%) probands using candidate gene panel analysis, which included BTK, CYBB, DKC1, DNAH11, DNAH5, IL2RG, NFKB2, PIK3CD and SH2D1A. Genotype-driven analysis identified pathogenic variants in two (8%) probands involving NF1 and PTPN11, while an additional five (20%) probands were found to have structural variants, including BTK, LRBA and SH2D1A. In total, genetic analysis revealed causative variants in 60% of patients. Variants of uncertain significance were identified in four cases among three probands (12%).<\/p>\n

CONCLUSION: WGS facilitated the robust identification of causative genetic variants, including complex structural changes. These results suggest that employing WGS in patients suspected of IEIs could provide additional diagnostic yield.<\/p>\n

PMID:41275043<\/a> | DOI:10.1007\/s10875-025-01947-2<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"

J Clin Immunol. 2025 Nov 23. doi: 10.1007\/s10875-025-01947-2. Online ahead of print. ABSTRACT INTRODUCTION: Inborn errors of immunity (IEIs) constitute a diverse group of more than 500 disorders resulting from pathogenic variants in over 500 causative genes, with most being monogenic diseases. The use of exome sequencing based on next-generation sequencing technologies has significantly advanced … 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":[69,42],"tags":[],"class_list":["post-49361","post","type-post","status-publish","format-standard","hentry","category-journal-of-clinical-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/49361","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=49361"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/49361\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=49361"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=49361"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=49361"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}