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However, only one causative mutation (c.58T\u2009&gt;\u2009C, p.Y20H) in the\n                    <jats:italic>TFRC<\/jats:italic>\n                    gene coding for TfR1 has been reported so far. We herein identified a new disease-causing homozygous germline mutation in the\n                    <jats:italic>TFRC<\/jats:italic>\n                    gene (c.64C\u2009&gt;\u2009T, p.R22W) (referred to as TfR1\n                    <jats:sup>R22W<\/jats:sup>\n                    from now on) in a Turkish patient with combined immunodeficiency (CID). TfR1\n                    <jats:sup>R22W<\/jats:sup>\n                    results in impaired TfR1 internalization similar to previously defined TfR1\n                    <jats:sup>Y20H<\/jats:sup>\n                    mutation. We found that TfR1\n                    <jats:sup>R22W<\/jats:sup>\n                    is associated with severely restricted B and T lymphocyte clonal diversity and impaired T cell activation and cytokine production as well as defective mitochondrial oxidative phosphorylation in helper T cells. In addition, circulating NK, Treg, and MAIT cell populations were significantly decreased in the patient. Using whole transcriptome analysis, we found dysregulated immune homeostasis and novel biological processes associated with TfR1\n                    <jats:sup>R22W<\/jats:sup>\n                    . We also identified a considerable expansion of circulating low-density neutrophils (LDNs) in patient\u2019s PBMCs. Overall, TfR1\n                    <jats:sup>R22W<\/jats:sup>\n                    mutation expands the current understanding of the IEI associated with TfR1 dysfunction and provides new insights underlying impaired immune function, lymphocyte diversity, and granulocyte homeostasis.\n                  <\/jats:p>","DOI":"10.1007\/s10875-024-01658-0","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T08:50:43Z","timestamp":1706172643000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A Novel Homozygous Germline Mutation in Transferrin Receptor 1 (TfR1) Leads to Combined Immunodeficiency and Provides New Insights into Iron-Immunity Axis"],"prefix":"10.1007","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9458-3953","authenticated-orcid":false,"given":"\u00dcmran","family":"Aba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9708-5490","authenticated-orcid":false,"given":"\u0130brahim Cemal","family":"Maslak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0726-5004","authenticated-orcid":false,"given":"Canberk","family":"\u0130p\u015fir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2305-210X","authenticated-orcid":false,"given":"Damla","family":"Pehlivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3422-3184","authenticated-orcid":false,"given":"Nicholas I.","family":"Warnock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5709-857X","authenticated-orcid":false,"given":"Damon J.","family":"Tumes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7457-9164","authenticated-orcid":false,"given":"G\u00f6khan","family":"Cildir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9398-8465","authenticated-orcid":false,"given":"Baran","family":"Erman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,25]]},"reference":[{"issue":"10","key":"1658_CR1","doi-asserted-by":"publisher","first-page":"3711","DOI":"10.1182\/blood-2003-04-1086","volume":"102","author":"RM Ned","year":"2003","unstructured":"Ned RM, Swat W, Andrews NC. 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Approval was granted by the local Ethics Committee of the Hacettepe University (GO 20\/407).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"The authors affirm that the patient provided informed consent for publication of the images in Supplementary Figure\u00a02.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}],"article-number":"55"}}