{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:34:29Z","timestamp":1791408869752,"version":"4.3.3"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>ACKR1\/DARC\u2010associated neutropenia (ADAN), resulting from homozygosity for a single nucleotide polymorphism (SNP) in the <jats:italic>ACKR1\/DARC<\/jats:italic> gene (rs2814778), is a common cause of benign neutropenia that primarily affects individuals of African and Jewish Yemenite descent. We aimed to characterize ADAN in pediatric patients in Israel, given its ethnically diverse population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>We assessed children with isolated neutropenia treated during 2018\u20132023 at one pediatric center, for the <jats:italic>ACKR1\/DARC<\/jats:italic> polymorphism, using Sanger sequencing or targeted next\u2010generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 115 patients evaluated, 49 (42.6%) were diagnosed with ADAN; of these, 29 (59%) had absolute neutrophil counts in the severe range (0\u20130.5\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/L) at diagnosis. The allele distribution revealed 37% of Muslim Arab and 61% of Jewish origin. Yemenite, Ethiopian, Mediterranean, Asian, and European ancestry were included; 59% had a family history of neutropenia. The median age at the first neutropenia detection was 1.2\u00a0years; 91.8% were identified during routine blood counts. The median absolute neutrophil count at diagnosis was 0.5\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/L (interquartile range: 0.3). An increased susceptibility to infections was not found either before or during the median follow\u2010up period of 2.5\u00a0years (interquartile range: 1.54) after the diagnosis of ADAN. In 34 patients (72.3%), neutrophil counts were in the normal range during febrile illnesses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We identified ADAN in individuals of variable ethnicities, almost half with severe neutropenia. We recommend testing for ADAN in all children with isolated neutropenia without severe infections. Homozygosity for the <jats:italic>ACKR1\/DARC<\/jats:italic> rs2814778 SNP may obviate the need for further investigation, follow\u2010up, or treatment in specific clinical scenarios.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.31430","type":"journal-article","created":{"date-parts":[[2024,11,7]],"date-time":"2024-11-07T06:19:23Z","timestamp":1730960363000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical and Laboratory Characteristics of Pediatric Patients With <i>ACKR1\/DARC<\/i>\u2010Associated Neutropenia"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1986-4146","authenticated-orcid":false,"given":"Lital","family":"Oz\u2010Alcalay","sequence":"first","affiliation":[{"name":"Department of Internal Pediatrics A Schneider Children's Medical Center of Israel  Petach Tikva Israel"},{"name":"School of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1680-2388","authenticated-orcid":false,"given":"Orna","family":"Steinberg\u2010Shemer","sequence":"additional","affiliation":[{"name":"School of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"The Rina Zaizov Hematology\/Oncology Division Schneider Children's Medical Center of Israel  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5144-4993","authenticated-orcid":false,"given":"Eyal","family":"Elron","sequence":"additional","affiliation":[{"name":"The Rina Zaizov Hematology\/Oncology Division Schneider Children's Medical Center of Israel  Petach Tikva Israel"},{"name":"Pediatric Genetic Unit Schneider Children's Medical Center of Israel  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Dvori","sequence":"additional","affiliation":[{"name":"School of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"The Rina Zaizov Hematology\/Oncology Division Schneider Children's Medical Center of Israel  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3495-7578","authenticated-orcid":false,"given":"Sarah","family":"Elitzur","sequence":"additional","affiliation":[{"name":"School of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"The Rina Zaizov Hematology\/Oncology Division Schneider Children's Medical Center of Israel  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Dgany","sequence":"additional","affiliation":[{"name":"The Rina Zaizov Hematology\/Oncology Division Schneider Children's Medical Center of Israel  Petach Tikva Israel"},{"name":"Pediatric Hematology Laboratory Felsenstein Medical Research Center  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Noy\u2010Lotan","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Laboratory Felsenstein Medical Research Center  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Krasnov","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Laboratory Felsenstein Medical Research Center  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Tamary","sequence":"additional","affiliation":[{"name":"School of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"The Rina Zaizov Hematology\/Oncology Division Schneider Children's Medical Center of Israel  Petach Tikva Israel"},{"name":"Pediatric Hematology Laboratory Felsenstein Medical Research Center  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafna","family":"Brik\u2010Simon","sequence":"additional","affiliation":[{"name":"School of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"The Rina Zaizov Hematology\/Oncology Division Schneider Children's Medical Center of Israel  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Yacobovich","sequence":"additional","affiliation":[{"name":"School of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"The Rina Zaizov Hematology\/Oncology Division Schneider Children's Medical Center of Israel  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0033-3425","authenticated-orcid":false,"given":"Oded","family":"Gilad","sequence":"additional","affiliation":[{"name":"School of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"The Rina Zaizov Hematology\/Oncology Division Schneider Children's Medical Center of Israel  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.14197"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-200701000-00006"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14887"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/HS9.0000000000000872"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000528"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010400"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-194103000-00013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1988.tb01192.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2019.06.003"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000360"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2019.01.009"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2326-9-3"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2007.09.003"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25813"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07335.x"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15730"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006560"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.27361"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3763"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020008600"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007679"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/lc.1999.v133.a94931"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1265"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-014-2465-5"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13345"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007680"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.280116"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2022.01.025"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25251"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-146-7-200704030-00004"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/moh.0000000000000208"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14677"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2013.06.010"},{"key":"e_1_2_8_35_1","volume-title":"StatPearls","author":"Tahir N.","year":"2023"},{"issue":"5","key":"e_1_2_8_36_1","first-page":"297","article-title":"The Epidemiology of Benign Leukopenia in Yemenite Jews","volume":"29","author":"Weingarten M. A.","year":"1993","journal-title":"Israel Journal of Medical Sciences"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.31430","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T13:21:01Z","timestamp":1739971261000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.31430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,6]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/pbc.31430"],"URL":"https:\/\/doi.org\/10.1002\/pbc.31430","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,6]]},"assertion":[{"value":"2024-06-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e31430"}}