{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:40:10Z","timestamp":1780080010204,"version":"3.54.0"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,12]],"date-time":"2020-04-12T00:00:00Z","timestamp":1586649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002350","name":"St. Giles Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002350","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder (PID) affecting NADPH oxidase activity. The rarest form of the disease is considered to be caused by <jats:italic>NCF2<\/jats:italic> gene bi\u2010allelic variant. Here, we report the clinical and molecular characterization of a patient presenting with early\u2010onset severe disease due to bi\u2010allelic <jats:italic>NCF2<\/jats:italic> variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gene mutational analysis was performed by whole\u2010exome and Sanger sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient presented with a history of fever and rash since the age of 1\u00a0month, followed by destructive osteomyelitis and necrotizing lymphadenopathy. The patient received the Bacillus Calmette\u2010Gu\u00e9rin (BCG) vaccine at birth; she was subsequently diagnosed with disseminated BCG infection. Whole\u2010exome sequencing identified a private (unreported) homozygous variant in <jats:italic>NCF2<\/jats:italic> (c.290C\u00a0&gt;\u00a0A) that results in a nonconservative change, p.Ala97Asp, in the p67<jats:italic><jats:sup>phox<\/jats:sup><\/jats:italic> protein. The variant is located in the third helix of the TRP domain, which is crucial for the binding of GTPase RAC2 to the NADPH oxidase complex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We identified a novel <jats:italic>NCF2<\/jats:italic> variant located in the region interacting with RAC2 that is linked to a severe and early CGD phenotype in the setting of disseminated BCG infection. Our findings support postponing BCG vaccination until 6\u201312\u00a0months of age and after PID assessment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1237","type":"journal-article","created":{"date-parts":[[2020,4,13]],"date-time":"2020-04-13T03:44:27Z","timestamp":1586749467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A novel variant in the neutrophil cytosolic factor 2 (<i>NCF2<\/i>) gene results in severe disseminated BCG infectious disease: A clinical report and literature review"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7315-6581","authenticated-orcid":false,"given":"Suzan A.","family":"AlKhater","sequence":"first","affiliation":[{"name":"Department of Pediatrics King Fahad Hospital of University, Al-Khobar Imam Abdulrahman Bin Faisal University College of Medicine Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Deswarte","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases Necker Branch INSERM U1163 Necker Hospital for Sick Children Paris France"},{"name":"Paris University Imagine Institute Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Laurent","family":"Casanova","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases Necker Branch INSERM U1163 Necker Hospital for Sick Children Paris France"},{"name":"Paris University Imagine Institute Paris France"},{"name":"St Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch The Rockefeller University New York NY USA"},{"name":"Howard Hughes Medical Institute New York NY USA"},{"name":"Pediatric Hematology and Immunology Unit Assistance Publique\u2010H\u00f4pitaux de Paris Necker Hospital for Sick Children Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacinta","family":"Bustamante","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Infectious Diseases Necker Branch INSERM U1163 Necker Hospital for Sick Children Paris France"},{"name":"Paris University Imagine Institute Paris France"},{"name":"St Giles Laboratory of Human Genetics of Infectious Diseases Rockefeller Branch The Rockefeller University New York NY USA"},{"name":"Center for the Study of Primary Immunodeficiencies Necker Hospital for Sick Children AP\u2010HP Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-017-2499-7"},{"issue":"3","key":"e_1_2_8_3_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.4103\/2230-8229.96520","article-title":"Approach to the child with recurrent infections","volume":"16","author":"Alkhater S. 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