{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:40:31Z","timestamp":1790912431831,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T00:00:00Z","timestamp":1712793600000},"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":["European J of Haematology"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital neutropenias are characterized by severe infections and a high risk of myeloid transformation; the causative genes vary across ethnicities. The Israeli population is characterized by an ethnically diverse population with a high rate of consanguinity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the clinical and genetic spectrum of congenital neutropenias in Israel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included individuals with congenital neutropenias listed in the Israeli Inherited Bone Marrow Failure Registry. Sanger sequencing was performed for <jats:italic>ELANE<\/jats:italic> or <jats:italic>G6PC3<\/jats:italic>, and patients with wild\u2010type <jats:italic>ELANE\/G6PC3<\/jats:italic> were referred for next\u2010generation sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010five patients with neutropenia were included. Of 51 patients with severe congenital neutropenia, 34 were genetically diagnosed, most commonly with variants in <jats:italic>ELANE<\/jats:italic> (15 patients). Nine patients had biallelic variants in <jats:italic>G6PC3<\/jats:italic>, all of consanguineous Muslim Arab origin. Other genes involved were <jats:italic>SRP54<\/jats:italic>, <jats:italic>JAGN1<\/jats:italic>, <jats:italic>TAZ<\/jats:italic>, and <jats:italic>SLC37A4<\/jats:italic>. Seven patients had cyclic neutropenia, all with pathogenic variants in <jats:italic>ELANE<\/jats:italic>, and seven had Shwachman\u2013Diamond syndrome caused by biallelic <jats:italic>SBDS<\/jats:italic> variants. Eight patients (12%) developed myeloid transformation, including six patients with an unknown underlying genetic cause. Nineteen (29%) patients underwent hematopoietic stem cell transplantation, mostly due to insufficient response to treatment with granulocyte\u2010colony stimulating factor or due to myeloid transformation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The genetic spectrum of congenital neutropenias in Israel is characterized by a high prevalence of <jats:italic>G6PC3<\/jats:italic> variants and an absence of <jats:italic>HAX1<\/jats:italic> mutations. Similar to other registries, for 26% of the patients, a molecular diagnosis was not achieved. However, myeloid transformation was common in this group, emphasizing the need for close follow\u2010up.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.14197","type":"journal-article","created":{"date-parts":[[2024,4,11]],"date-time":"2024-04-11T07:45:58Z","timestamp":1712821558000},"page":"146-162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic backgrounds and clinical characteristics of congenital neutropenias in <scp>Israel<\/scp>"],"prefix":"10.1111","volume":"113","author":[{"given":"Lital","family":"Yeshareem","sequence":"first","affiliation":[{"name":"Kipper Institute of Allergy and Immunology Schneider Children's Medical Center of Israel  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-5694","authenticated-orcid":false,"given":"Joanne","family":"Yacobovich","sequence":"additional","affiliation":[{"name":"Department of 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