{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:14:11Z","timestamp":1762254851065,"version":"3.37.3"},"reference-count":5,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:00:00Z","timestamp":1716336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"BMBF-funded German Auto-Immunity Network","award":["197 01GM1910A","197 01GM1910A"],"award-info":[{"award-number":["197 01GM1910A","197 01GM1910A"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["CRC237 369799452\/B21 and CRC237 369799452\/A11","CRC237 369799452\/A06","CIBSS\u2014EXC-21899\u2014Project ID 390939984"],"award-info":[{"award-number":["CRC237 369799452\/B21 and CRC237 369799452\/A11","CRC237 369799452\/A06","CIBSS\u2014EXC-21899\u2014Project ID 390939984"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Universit\u00e4tsklinikum Freiburg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in genes of the DNA polymerase complex have been linked to impaired immunological function next to distinct syndromic features. Biallelic mutations in PRIM1 are associated with a primordial dwarfism syndrome with variable hypogammaglobulinemia. The disease is mostly lethal in infancy due to pulmonary infections as well as hepatic cirrhosis. We studied 3 novel patients with PRIM1-deficiency with a focus on immunological consequences. All three shared dysmorphic features including a prominent forehead, triangular face and bilateral cryptorchidism. P1 carried the novel homozygous PRIM1 splice variant c.103+2T&gt;G, allowing residual protein expression and associated with a mild clinical phenotype. P2 and P3 carried the known homozygous variant c.638+36C&gt;G and died in infancy. Paradoxically, B cell lymphopenia was most pronounced in P1. No other significant lymphocyte abnormalities were detected. Interestingly, all 3 patients showed variable, but intermittently excessive Type I interferon signatures. In summary, the B-cell deficiency in PRIM1-deficiency is markedly variable and the severity of syndromic manifestations is not predictive of the immunological phenotype. We highlight a potential contribution of pathological type I interferon activation to disease pathogenesis which warrants further investigations.<\/jats:p>","DOI":"10.1007\/s10875-024-01733-6","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T03:38:20Z","timestamp":1716349100000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Variable Syndromic Immunodeficiency in Patients with Biallelic PRIM1 Mutations"],"prefix":"10.1007","volume":"44","author":[{"given":"Vasil","family":"Toskov","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petra","family":"Kaiser-Labusch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min Ae","family":"Lee-Kirsch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"PRIM1 study group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Speckmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Ehl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9391-0761","authenticated-orcid":false,"given":"Oliver","family":"Wegehaupt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,5,22]]},"reference":[{"issue":"5","key":"1733_CR1","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/ni.3409","volume":"17","author":"P Starokadomskyy","year":"2016","unstructured":"Starokadomskyy P, et al. DNA polymerase-\u03b1 regulates the activation of type I interferons through cytosolic RNA:DNA synthesis. Nat Immunol. 2016;17(5):495\u2013504.","journal-title":"Nat Immunol"},{"issue":"10","key":"1733_CR2","doi-asserted-by":"publisher","first-page":"4194","DOI":"10.1172\/JCI128903","volume":"129","author":"CD Conde","year":"2019","unstructured":"Conde CD, et al. Polymerase \u03b4 deficiency causes syndromic immunodeficiency with replicative stress. J Clin Invest. 2019;129(10):4194\u2013206.","journal-title":"J Clin Invest"},{"issue":"6","key":"1733_CR3","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.ajhg.2018.10.024","volume":"103","author":"CV Logan","year":"2018","unstructured":"Logan CV, et al. DNA polymerase epsilon deficiency causes IMAGe syndrome with variable immunodeficiency. Am J Hum Genet. 2018;103(6):1038\u201344.","journal-title":"Am J Hum Genet"},{"issue":"21\u201322","key":"1733_CR4","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1101\/gad.340190.120","volume":"34","author":"DA Parry","year":"2020","unstructured":"Parry DA, et al. PRIM1 deficiency causes a distinctive primordial dwarfism syndrome. Genes Dev. 2020;34(21\u201322):1520\u201333.","journal-title":"Genes Dev"},{"issue":"21","key":"1733_CR5","doi-asserted-by":"publisher","first-page":"e125688","DOI":"10.1172\/jci.insight.125688","volume":"4","author":"P Starokadomskyy","year":"2019","unstructured":"Starokadomskyy P, et al. NK cell defects in X-linked pigmentary reticulate disorder. JCI Insight. 2019;4(21):e125688. https:\/\/doi.org\/10.1172\/jci.insight.125688","journal-title":"JCI Insight."}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-024-01733-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-024-01733-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-024-01733-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T08:15:08Z","timestamp":1719562508000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-024-01733-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,22]]},"references-count":5,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["1733"],"URL":"https:\/\/doi.org\/10.1007\/s10875-024-01733-6","relation":{},"ISSN":["0271-9142","1573-2592"],"issn-type":[{"type":"print","value":"0271-9142"},{"type":"electronic","value":"1573-2592"}],"subject":[],"published":{"date-parts":[[2024,5,22]]},"assertion":[{"value":"20 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"129"}}