{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:20:39Z","timestamp":1788956439797,"version":"build-2803163510"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T00:00:00Z","timestamp":1651536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>DNA ligase IV deficiency is a rare autosomal recessive disorder associated with impaired DNA repair mechanisms. Most patients with DNA repair defects present with neurologic deficits, combined immunodeficiency, bone marrow failure, and\/or hematologic neoplasia. We present 3 unrelated cases of ligase IV deficiency with different clinical presentations. Patient 1 presented at the age of 5 with bone marrow failure, dysmorphic features, and T and B lymphopenia. A compound heterozygous variant <jats:italic>L19W\/K635fs<\/jats:italic> in the <jats:italic>LIG4<\/jats:italic> gene was identified. Patient 2 presented at the age of 16 with recurrent infections. He had agammaglobulinemia and absent B cells. A homozygous <jats:italic>R278H<\/jats:italic> in the <jats:italic>LIG4<\/jats:italic> gene was identified. Patient 3 was referred for vitiligo and B-cell lymphopenia (low class-switched B cells) and hypogammaglobulinemia. Homozygous <jats:italic>R278H<\/jats:italic> in <jats:italic>LIG4<\/jats:italic> was also identified. In the last few years, the spectrum of clinical manifestations caused by ligase IV deficiency has widened, making it very difficult to establish an accurate clinical diagnosis. The use of NGS allows a proper diagnosis and provides a better prognosis and adequate family counseling.<\/jats:p>","DOI":"10.3389\/fimmu.2022.869728","type":"journal-article","created":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T07:57:28Z","timestamp":1651564648000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Case Report: Wide Spectrum of Manifestations of Ligase IV Deficiency: Report of 3 Cases"],"prefix":"10.3389","volume":"13","author":[{"given":"Ana Costa e","family":"Castro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Maia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Batalha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Parente","family":"Freixo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concei\u00e7\u00e3o","family":"Neves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Isabel","family":"Cordeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Farela","family":"Neves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13023-016-0520-1","article-title":"DNA Ligase IV Syndrome; A Review","volume":"11","author":"Altmann","year":"2016","journal-title":"Orphanet J Rare Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2018.00426","article-title":"Failing to Make Ends Meet: The Broad Clinical Spectrum of DNA Ligase IV Deficiency. 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