{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T15:25:44Z","timestamp":1767108344630},"reference-count":28,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,1,30]],"date-time":"2014-01-30T00:00:00Z","timestamp":1391040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>To describe the clinical profile and the prevalence of severe congenital neutropenia (SCN) and HAX1 mutations, so\u2010called Kostmann syndrome, in France.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Two pedigrees were identified from the French registry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included five subjects (three males), which represent 0.7% of the 759 SCN cases registered in France. The age at diagnosis was 0.3 years (range: 0.1\u20131.2 years) and the median age at the last follow\u2010up was 7.3 years (range: 1.2\u201317.8 years). A novel large homozygous deletion of the <jats:italic>HAX1<\/jats:italic> gene (exons 2\u20135) was found in one pedigree; while, a homozygous frameshift mutation was identified in exon 3 (c.430dupG, p.Val144fs) in the second pedigree. Severe bacterial infections were observed in four patients, including two cases of sepsis, one case of pancolitis, a lung abscess, and recurrent cellulitis and stomatitis. During routine follow\u2010up, the median neutrophil value was 0.16\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L, associated with monocytosis (2\u2009\u00d7\u200910<jats:sup>9<\/jats:sup>\/L). Bone marrow (BM) smears revealed a decrease of the granulocytic lineage with no mature myeloid cells above the myelocytes. One patient died at age 2 from neurological complications, while two other patients, including one who underwent a hematopoietic stem cell transplantation (HSCT) at age 5, are living with very severe neurological retardation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>SCN with <jats:italic>HAX1<\/jats:italic> mutations, is a rare sub type of congenital neutropenia, mostly observed in population from Sweden and Asia minor, associating frequently neurological retardation, when the mutations involved the B isoform of the protein. Pediatr Blood Cancer 2014;61:1041\u20131048. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.24964","type":"journal-article","created":{"date-parts":[[2014,1,30]],"date-time":"2014-01-30T12:33:34Z","timestamp":1391085214000},"page":"1041-1048","source":"Crossref","is-referenced-by-count":23,"title":["Neurological findings and genetic alterations in patients with Kostmann syndrome and <i>HAX1<\/i> mutations"],"prefix":"10.1002","volume":"61","author":[{"given":"Ga\u00eblle","family":"Roques","sequence":"first","affiliation":[{"name":"Service d'H\u00e9mato\u2010Oncologie P\u00e9diatrique APHP Hopital Trousseau Paris France"},{"name":"Service de p\u00e9diatrie CHU de Reims Reims France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martine","family":"Munzer","sequence":"additional","affiliation":[{"name":"Service de p\u00e9diatrie CHU de Reims Reims France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie\u2010Anne Carpentier","family":"Barthez","sequence":"additional","affiliation":[{"name":"Service de Neuro p\u00e9diatrie CHU de Tours Tours France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Beaufils","sequence":"additional","affiliation":[{"name":"AP\u2010HP, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re, D\u00e9partement de G\u00e9n\u00e9tique Universit\u00e9 Pierre et Marie Curie Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blandine","family":"Beaupain","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9mato\u2010Oncologie P\u00e9diatrique APHP Hopital Trousseau Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terry","family":"Flood","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine The Medical School Newcastle upon Tyne UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boris","family":"Keren","sequence":"additional","affiliation":[{"name":"AP\u2010HP, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re, D\u00e9partement de G\u00e9n\u00e9tique Universit\u00e9 Pierre et Marie Curie Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Bellann\u00e9\u2010Chantelot","sequence":"additional","affiliation":[{"name":"AP\u2010HP, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re, D\u00e9partement de G\u00e9n\u00e9tique Universit\u00e9 Pierre et Marie Curie Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean","family":"Donadieu","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9mato\u2010Oncologie P\u00e9diatrique APHP Hopital Trousseau Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,1,30]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"2861","article-title":"Heredit\u00e4r reticulos\u2014en ny systemsjukdom","volume":"47","author":"Kostmann R","year":"1950","journal-title":"Svenska L\u00e4kartideningen"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1956.tb06875.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1940"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-120667"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33748"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2008.01982.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-26"},{"key":"e_1_2_7_9_1","first-page":"45","article-title":"Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. 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