{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T19:43:03Z","timestamp":1788982983287,"version":"build-2803163510"},"reference-count":0,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:00:00Z","timestamp":1666310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Arch Allergy Immunol"],"published-print":{"date-parts":[[2023]]},"abstract":"<jats:p>Background: The diagnostic yield of next-generation sequencing (NGS) technologies in the diagnosis of monogenic inborn errors of immunity (IEI) remains limited, rarely exceeding 30%. Monoallelic pathogenic germline variants in cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) result in variable immunodeficiency and immune dysregulation. The genetic diagnosis of CTLA-4 insufficiency can affect follow-up procedures and may lead to consideration of treatment with CTLA-4-Ig. Objectives: The aim of the study was to identify the genetic cause of familial immunodeficiency and immune dysregulation in cases where single nucleotide variant analysis of short-read NGS data yielded no diagnostic result. Methods: Analysis of copy number variants (CNVs) was applied on short-read NGS data. Results: We identified a novel monoallelic deletion-insertion variant in CTLA-4 (c.445_568-544delinsTTTGCGATTG) resulting in familial autoimmunity. This is the second larger scale variant in CTLA-4, which despite consistently reduced expression of CTLA-4 displayed variable expressivity, ranging from typical juvenile idiopathic arthritis to common variable immunodeficiency-like immunodeficiency. Conclusions: Our report suggests the significance of integration of CNV analysis in routine evaluation of NGS, which may increase its diagnostic yield in IEI. <\/jats:p>","DOI":"10.1159\/000527051","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T21:00:35Z","timestamp":1666386035000},"page":"76-84","source":"Crossref","is-referenced-by-count":8,"title":["CTLA-4 Insufficiency due to a Novel CTLA-4 Deletion, Identified through Copy Number Variation Analysis"],"prefix":"10.1159","volume":"184","author":[{"given":"Lisa","family":"Olfe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3680-7450","authenticated-orcid":false,"given":"Sandra","family":"von Hardenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6658-3366","authenticated-orcid":false,"given":"Winfried","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Auber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Beier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignatius Ryan","family":"Adriawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faranaz","family":"Atschekzei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten","family":"Witte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0855-2945","authenticated-orcid":false,"given":"Georgios","family":"Sogkas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2022,10,21]]},"container-title":["International Archives of Allergy and Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/iaa\/article-pdf\/184\/1\/76\/3962956\/000527051.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/iaa\/article-pdf\/184\/1\/76\/3962956\/000527051.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:22:40Z","timestamp":1745421760000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000527051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,21]]},"references-count":0,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1,3]]},"published-print":{"date-parts":[[2023,1,12]]}},"URL":"https:\/\/doi.org\/10.1159\/000527051","archive":["Portico"],"relation":{},"ISSN":["1018-2438","1423-0097"],"issn-type":[{"value":"1018-2438","type":"print"},{"value":"1423-0097","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,21]]}}}