{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:26:16Z","timestamp":1784175976118,"version":"3.55.0"},"reference-count":40,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pollock Center for IBD","award":["private endowment"],"award-info":[{"award-number":["private endowment"]}]},{"name":"NIH","award":["R56-AI113274"],"award-info":[{"award-number":["R56-AI113274"]}]},{"DOI":"10.13039\/100000057","name":"National Institutes of General Medical Sciences","doi-asserted-by":"crossref","award":["T32-GM-65841"],"award-info":[{"award-number":["T32-GM-65841"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"crossref","award":["R01-AI120949"],"award-info":[{"award-number":["R01-AI120949"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:p>\n                    X-linked reticulate pigmentary disorder (XLPDR, Mendelian Inheritance in Man #301220) is a rare syndrome characterized by recurrent infections and sterile multiorgan inflammation. The syndrome is caused by an intronic mutation in\n                    <jats:italic>POLA1,<\/jats:italic>\n                    the gene encoding the catalytic subunit of DNA polymerase-\u03b1 (Pol-\u03b1), which is responsible for Okazaki fragment synthesis during DNA replication. Reduced\n                    <jats:italic>POLA1<\/jats:italic>\n                    expression in this condition triggers spontaneous type I interferon expression, which can be linked to the autoinflammatory manifestations of the disease. However, the history of recurrent infections in this syndrome is as yet unexplained. Here we report that patients with XLPDR have reduced NK cell cytotoxic activity and decreased numbers of NK cells, particularly differentiated, stage V, cells (CD3\n                    <jats:sup>\u2013<\/jats:sup>\n                    CD56\n                    <jats:sup>dim<\/jats:sup>\n                    ). This phenotype is reminiscent of hypomorphic mutations in\n                    <jats:italic>MCM4<\/jats:italic>\n                    , which encodes a component of the minichromosome maintenance (MCM) helicase complex that is functionally linked to Pol-\u03b1 during the DNA replication process. We find that POLA1 deficiency leads to MCM4 depletion and that both can impair NK cell natural cytotoxicity and show that this is due to a defect in lytic granule polarization. Altogether, our study provides mechanistic connections between Pol-\u03b1 and the MCM complex and demonstrates their relevance in NK cell function.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.125688","type":"journal-article","created":{"date-parts":[[2019,10,31]],"date-time":"2019-10-31T11:01:33Z","timestamp":1572519693000},"source":"Crossref","is-referenced-by-count":22,"title":["NK cell defects in X-linked pigmentary reticulate disorder"],"prefix":"10.1172","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9848-9187","authenticated-orcid":true,"given":"Petro","family":"Starokadomskyy","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5060-8899","authenticated-orcid":true,"given":"Katelynn M.","family":"Wilton","sequence":"additional","affiliation":[{"name":"Department 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USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Gil-Krzewska","sequence":"additional","affiliation":[{"name":"Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Peterson","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa N.","family":"Kinch","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1593-6712","authenticated-orcid":true,"given":"Luis","family":"Rohena","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics, San Antonio Military Medical Center, San Antonio, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Grunebaum","sequence":"additional","affiliation":[{"name":"Division of Immunology and Allergy and Department of Pediatrics, Developmental and Stem Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R.","family":"Zinn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA."},{"name":"Eugene McDermott Center for Human Growth and 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