{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:46:01Z","timestamp":1753868761553,"version":"3.41.2"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009193","name":"Marsden Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009193","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019168","name":"Starship Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019168","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp; Trans Imm"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Dominant\u2010activating (DA) lesions in <jats:italic>RAC2<\/jats:italic> have been reported in 18 individuals to date. Some have required haematopoietic stem cell transplantation (HSCT) for their (severe) combined immunodeficiency syndrome phenotype. We aimed to investigate clinical and cellular features of a kindred harbouring a\u00a0novel variant in <jats:italic>RAC2<\/jats:italic> p.Ile21Ser (I21S) to better understand DA\u00a0lesions' phenotypic spectrum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical and immunological information was collated for seven living individuals from the same kindred with <jats:italic>RAC2<\/jats:italic> p.I21S. We evaluated neutrophil morphology, RAC2 protein expression and superoxide production using freshly isolated neutrophils stimulated with phorbol\u201012\u2010myristate\u201013\u2010acetate (PMA) and N\u2010formyl\u2010MetLeuPhe (fMLP).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patient 1 (P1, aged 11, male) has a history of bacterial suppurative otitis media, viral and bacterial cutaneous infections. P1's siblings (P2, P3), mother (P4), maternal aunt (P5) and uncle (P6) have similar infection histories. P1's maternal cousin (P7) presented with Burkitt's lymphoma at age 9. All affected individuals are alive and none has required HSCT to date. They have chronic lymphopenia affecting the CD4<jats:sup>+<\/jats:sup>T and B\u2010cell compartments. P1\u20133 have isolated reduction in IgM levels whereas the adults universally have normal immunoglobulins. Specific antibody responses are preserved. Affected individuals have neutrophil vacuolation, and their neutrophils have enhanced superoxide production compared to healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>RAC2<\/jats:italic> p.I21S is an activating variant causing notable morphological and functional abnormalities similar to other reported DA mutations. This novel variant expands the broad clinical phenotypic spectrum of <jats:italic>RAC2<\/jats:italic> DA lesions, emphasising the need to\u00a0tailor clinical management according to patients' disease phenotype and severity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cti2.1493","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T11:35:04Z","timestamp":1708947304000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic spectrum in a family with a novel <i>RAC2<\/i> p.I21S dominant\u2010activating mutation"],"prefix":"10.1002","volume":"13","author":[{"given":"Louisa","family":"Ashby","sequence":"first","affiliation":[{"name":"M\u0101tai H\u0101ora \u2013 Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science University of Otago Christchurch  Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Auckland City Hospital  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Winterbourn","sequence":"additional","affiliation":[{"name":"M\u0101tai H\u0101ora \u2013 Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science University of Otago Christchurch  Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"See\u2010Tarn","family":"Woon","sequence":"additional","affiliation":[{"name":"LabPLUS Te Toka Tumai, Te Whatu Ora  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Keating","sequence":"additional","affiliation":[{"name":"Canterbury Health Laboratories Te Whatu Ora  Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raoul","family":"Heller","sequence":"additional","affiliation":[{"name":"Genetic Health Service NZ \u2013 Northern Hub, Te Toka Tumai  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rohan","family":"Ameratunga","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology Auckland City Hospital  Auckland New Zealand"},{"name":"LabPLUS Te Toka Tumai, Te Whatu Ora  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ignatius","family":"Chua","sequence":"additional","affiliation":[{"name":"Canterbury Health Laboratories Te Whatu Ora  Christchurch New Zealand"},{"name":"Christchurch Hospital Te Whatu Ora  Christchurch New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7412-9761","authenticated-orcid":false,"given":"Kuang\u2010Chih","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Starship Child Health Te Whatu Ora  Auckland New Zealand"},{"name":"Department of Paediatrics: Child and Youth Health, Faculty of Medical and Health Sciences University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.5MR0520-194RR"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00500-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-886028"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2019.01.001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2019.05.003"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2019.108248"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00915-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.230250"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01288-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01373-8"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00761"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/cdli.3.6.722-726.1996"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000553"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0154-9_12"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0154-9_3"}],"container-title":["Clinical &amp; Translational Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cti2.1493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T11:51:31Z","timestamp":1708948291000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cti2.1493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/cti2.1493"],"URL":"https:\/\/doi.org\/10.1002\/cti2.1493","archive":["Portico"],"relation":{},"ISSN":["2050-0068","2050-0068"],"issn-type":[{"type":"print","value":"2050-0068"},{"type":"electronic","value":"2050-0068"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2024-01-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1493"}}