{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:03:33Z","timestamp":1790471013622,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Regulation of the actin cytoskeleton is crucial for normal development and function of the immune system, as evidenced by the severe immune abnormalities exhibited by patients bearing inactivating mutations in the Wiskott\u2013Aldrich syndrome protein (WASP), a key regulator of actin dynamics. WASP exerts its effects on actin dynamics through a multisubunit complex termed Arp2\/3. Despite the critical role played by Arp2\/3 as an effector of WASP-mediated control over actin polymerization, mutations in protein components of the Arp2\/3 complex had not previously been identified as a cause of immunodeficiency. Here, we describe two brothers with hematopoietic and immunologic symptoms reminiscent of Wiskott\u2013Aldrich syndrome (WAS). However, these patients lacked mutations in any of the genes previously associated with WAS. Whole-exome sequencing revealed a homozygous 2 bp deletion, n.c.G623DEL-TC (p.V208VfsX20), in Arp2\/3 complex component ARPC1B that causes a frame shift resulting in premature termination. Modeling of the disease in zebrafish revealed that ARPC1B plays a critical role in supporting T cell and thrombocyte development. Moreover, the defects in development caused by ARPC1B loss could be rescued by the intact human ARPC1B ortholog, but not by the p.V208VfsX20 variant identified in the patients. Moreover, we found that the expression of ARPC1B is restricted to hematopoietic cells, potentially explaining why a mutation in ARPC1B has now been observed as a cause of WAS, whereas mutations in other, more widely expressed, components of the Arp2\/3 complex have not been observed.<\/jats:p>","DOI":"10.4049\/jimmunol.1700460","type":"journal-article","created":{"date-parts":[[2017,11,10]],"date-time":"2017-11-10T17:10:14Z","timestamp":1510333814000},"page":"4036-4045","source":"Crossref","is-referenced-by-count":83,"title":["Disruption of Thrombocyte and T Lymphocyte Development by a Mutation in <i>ARPC1B<\/i>"],"prefix":"10.1093","volume":"199","author":[{"given":"Raz","family":"Somech","sequence":"first","affiliation":[{"name":"Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]},{"name":"The Wohl Institute for Translational Medicine, Sheba Medical Center , Tel Hashomer, Tel Aviv 52621,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atar","family":"Lev","sequence":"additional","affiliation":[{"name":"Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]},{"name":"The Wohl Institute for Translational Medicine, Sheba Medical Center , Tel Hashomer, Tel Aviv 52621,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8648-5253","authenticated-orcid":false,"given":"Yu Nee","family":"Lee","sequence":"additional","affiliation":[{"name":"Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]},{"name":"The Wohl Institute for Translational Medicine, Sheba Medical Center , Tel Hashomer, Tel Aviv 52621,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amos J","family":"Simon","sequence":"additional","affiliation":[{"name":"Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]},{"name":"The Wohl Institute for Translational Medicine, Sheba Medical Center , Tel Hashomer, Tel Aviv 52621,","place":["Israel"]},{"name":"Hematology Laboratory, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ortal","family":"Barel","sequence":"additional","affiliation":[{"name":"The Wohl Institute for Translational Medicine, Sheba Medical Center , Tel Hashomer, Tel Aviv 52621,","place":["Israel"]},{"name":"Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginette","family":"Schiby","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Avivi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Barshack","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Blood Cell Development and Function Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiejing","family":"Yin","sequence":"additional","affiliation":[{"name":"Blood Cell Development and Function Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0225-0586","authenticated-orcid":false,"given":"Minshi","family":"Wang","sequence":"additional","affiliation":[{"name":"Blood Cell Development and Function Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibin","family":"Yang","sequence":"additional","affiliation":[{"name":"Blood Cell Development and Function Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7298-1213","authenticated-orcid":false,"given":"Jennifer","family":"Rhodes","sequence":"additional","affiliation":[{"name":"Blood Cell Development and Function Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nufar","family":"Marcus","sequence":"additional","affiliation":[{"name":"Allergy and Immunology Unit, Schneider Children\u2019s Medical Center of Israel, Felsenstein Medical Research Center, Kipper Institute of Immunology, Petach Tikva, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 4920235,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben-Zion","family":"Garty","sequence":"additional","affiliation":[{"name":"Allergy and Immunology Unit, Schneider Children\u2019s Medical Center of Israel, Felsenstein Medical Research Center, Kipper Institute of Immunology, Petach Tikva, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 4920235,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6352-6956","authenticated-orcid":false,"given":"Jerry","family":"Stein","sequence":"additional","affiliation":[{"name":"Bone Marrow Transplantation Unit, Schneider Children\u2019s Medical Center of Israel, Petach Tikva, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 4920235,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ninette","family":"Amariglio","sequence":"additional","affiliation":[{"name":"The Wohl Institute for Translational Medicine, Sheba Medical Center , Tel Hashomer, Tel Aviv 52621,","place":["Israel"]},{"name":"Hematology Laboratory, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]},{"name":"Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]},{"name":"The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat Gan 52900,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon","family":"Rechavi","sequence":"additional","affiliation":[{"name":"The Wohl Institute for Translational Medicine, Sheba Medical Center , Tel Hashomer, Tel Aviv 52621,","place":["Israel"]},{"name":"Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel Aviv University , Tel Aviv 52621,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0792-3188","authenticated-orcid":false,"given":"David L","family":"Wiest","sequence":"additional","affiliation":[{"name":"Blood Cell Development and Function Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Blood Cell Development and Function Program, Fox Chase Cancer Center , Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,12,15]]},"reference":[{"key":"2025030614544051000_r1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.tcb.2016.08.001","article-title":"The diverse family of Arp2\/3 complexes","volume":"27","author":"Pizarro-Cerd\u00e1","year":"2017","journal-title":"Trends Cell 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Soc. Trans."},{"key":"2025030614544051000_r3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ceb.2016.04.005","article-title":"Function and regulation of the Arp2\/3 complex during cell migration in diverse environments","volume":"42","author":"Swaney","year":"2016","journal-title":"Curr. Opin. Cell Biol."},{"key":"2025030614544051000_r4","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/0092-8674(94)90528-2","article-title":"Isolation of a novel gene mutated in Wiskott-Aldrich syndrome","volume":"78","author":"Derry","year":"1994","journal-title":"Cell"},{"key":"2025030614544051000_r5","volume-title":"GeneReviews\u00ae.","author":"Chandra","year":"1993"},{"key":"2025030614544051000_r6","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1084\/jem.20110896","article-title":"A novel primary human immunodeficiency due to deficiency in the WASP-interacting protein WIP","volume":"209","author":"Lanzi","year":"2012","journal-title":"J. Exp. Med."},{"key":"2025030614544051000_r7","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/imr.12114","article-title":"Actin cytoskeletal defects in immunodeficiency","volume":"256","author":"Moulding","year":"2013","journal-title":"Immunol. Rev."},{"key":"2025030614544051000_r8","doi-asserted-by":"crossref","first-page":"6185","DOI":"10.1128\/MCB.00018-06","article-title":"Sleeping beauty transposon-based phenotypic analysis of mice: lack of Arpc3 results in defective trophoblast outgrowth","volume":"26","author":"Yae","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"2025030614544051000_r9","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.jaci.2016.09.061","article-title":"Combined immunodeficiency with severe inflammation and allergy caused by ARPC1B deficiency","volume":"140","author":"Kuijpers","year":"2017","journal-title":"J. Allergy Clin. 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Commun."},{"key":"2025030614544051000_r25","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1371\/journal.pgen.0010047","article-title":"Evolutionary comparison provides evidence for pathogenicity of RMRP mutations","volume":"1","author":"Bonaf\u00e9","year":"2005","journal-title":"PLoS Genet."},{"key":"2025030614544051000_r26","doi-asserted-by":"crossref","first-page":"E7128","DOI":"10.1073\/pnas.1521651112","article-title":"Severe infectious diseases of childhood as monogenic inborn errors of immunity","volume":"112","author":"Casanova","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030614544051000_r27","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1111\/bjh.14535","article-title":"The genomics of inherited bone marrow failure: from mechanism to the clinic","volume":"177","author":"Wegman-Ostrosky","year":"2017","journal-title":"Br. J. Haematol."},{"key":"2025030614544051000_r28","first-page":"340","article-title":"Next generation sequencing reveals skewing of the T and B cell receptor repertoires in patients with wiskott-Aldrich syndrome","volume":"5","author":"O\u2019Connell","year":"2014","journal-title":"Front. Immunol."},{"key":"2025030614544051000_r29","doi-asserted-by":"crossref","first-page":"E3834","DOI":"10.1073\/pnas.1517798113","article-title":"Role and structural mechanism of WASP-triggered conformational changes in branched actin filament nucleation by Arp2\/3 complex","volume":"113","author":"Rodnick-Smith","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030614544051000_r30","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/ped.12819","article-title":"WASP-WIP complex in the molecular pathogenesis of Wiskott-Aldrich syndrome","volume":"58","author":"Sasahara","year":"2016","journal-title":"Pediatr. Int."},{"key":"2025030614544051000_r31","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/ncb3286","article-title":"Isoform diversity in the Arp2\/3 complex determines actin filament dynamics","volume":"18","author":"Abella","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"2025030614544051000_r32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1080\/08916930310001624656","article-title":"Common patterns of B cell perturbation and expanded V4-34 immunoglobulin gene usage in autoimmunity and infection","volume":"37","author":"Mockridge","year":"2004","journal-title":"Autoimmunity"},{"key":"2025030614544051000_r33","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1136\/annrheumdis-2012-202861","article-title":"Rheumatoid arthritis synovial tissue harbours dominant B-cell and plasma-cell clones associated with autoreactivity","volume":"73","author":"Doorenspleet","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"2025030614544051000_r34","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.it.2011.09.005","article-title":"T cell receptor signalling in \u03b3\u03b4 cell development: strength isn\u2019t everything","volume":"32","author":"Turchinovich","year":"2011","journal-title":"Trends Immunol."},{"key":"2025030614544051000_r35","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1172\/JCI60434","article-title":"Hooked! modeling human disease in zebrafish","volume":"122","author":"Santoriello","year":"2012","journal-title":"J. Clin. 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