{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:04:46Z","timestamp":1791065086085,"version":"4.1.0"},"reference-count":24,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>Severe congenital neutropenia (SCN), also known as Kostmann syndrome (SCN3, OMIM 610738), includes a variety of haematological disorders caused by different genetic abnormalities. Mutations in <jats:italic>ELA2<\/jats:italic> are most often the cause in autosomal dominant or sporadic forms. Recently, mutations in <jats:italic>HAX1<\/jats:italic> have been identified as the cause of some autosomal recessive forms of SCN, including those present in the original pedigree first reported by Kostmann. We sought to determine the relationship between <jats:italic>HAX1<\/jats:italic> gene mutations and the clinical characteristics of Japanese cases of SCN.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods:<\/jats:title>\n                  <jats:p>The genes implicated in SCN (<jats:italic>ELA2, HAX1, Gfi-1<\/jats:italic>, <jats:italic>WAS<\/jats:italic>, and <jats:italic>P14<\/jats:italic>) were analysed in 18 Japanese patients with SCN. The clinical features of these patients were obtained from medical records. Immunoblotting of HAX1 was performed on cell extracts from peripheral blood leucocytes from patients and\/or their parents.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>We found five patients with HAX1 deficiency and 11 patients with mutations in the <jats:italic>ELA2<\/jats:italic> gene. In HAX1 deficiency, a homozygous single base pair substitution (256C&gt;T), which causes the nonsense change R86X, was identified in three affected individuals. Two sibling patients showed a compound heterozygous mutation consisting of a single base pair substitution (256C&gt;T) and a 59 bp deletion at nucleotides 376\u2013434. There was no detectable phenotype in any heterozygous carrier. All patients with HAX1 deficiency had experienced developmental delay. Three patients carrying R86X also suffered from epileptic seizures. In contrast, no SCN patient with heterozygous mutations in the <jats:italic>ELA2<\/jats:italic> gene suffered from any neurodevelopmental abnormality.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>These findings suggest that the R86X mutation in the <jats:italic>HAX1<\/jats:italic> gene is an abnormality in Japanese SCN patients with HAX1 deficiency and may lead to neurodevelopmental abnormalities and severe myelopoietic defects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2008.058297","type":"journal-article","created":{"date-parts":[[2008,7,9]],"date-time":"2008-07-09T01:02:27Z","timestamp":1215565347000},"page":"802-807","source":"Crossref","is-referenced-by-count":45,"title":["Neurodevelopmental abnormalities associated with severe congenital neutropenia due to the R86X mutation in the <i>HAX1<\/i> gene"],"prefix":"10.1136","volume":"45","author":[{"given":"N","family":"Ishikawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Okada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Miki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Shirao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Kihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Tsumura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Ohtsubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Yasunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Matsubara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Sako","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Shiohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Takihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2008,7,8]]},"reference":[{"key":"2025100510455477000_45.12.802.1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2006.04.004"},{"key":"2025100510455477000_45.12.802.2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21282"},{"key":"2025100510455477000_45.12.802.3","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1182\/blood.V96.7.2317","article-title":"Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia.","volume":"96","author":"Dale","year":"2000","journal-title":"Blood"},{"key":"2025100510455477000_45.12.802.4","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0060"},{"key":"2025100510455477000_45.12.802.5","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3518"},{"key":"2025100510455477000_45.12.802.6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-08-019166"},{"key":"2025100510455477000_45.12.802.7","first-page":"1032","article-title":"A comparison of the defective granulopoiesis in childhood cyclic neutropenia and in severe congenital neutropenia.","volume":"908","author":"Sera","year":"2005","journal-title":"Haematologica"},{"key":"2025100510455477000_45.12.802.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng1940"},{"key":"2025100510455477000_45.12.802.9","doi-asserted-by":"crossref","unstructured":"Kostmann R . Infantile genetic agranulocytosis. A review with presentation of ten new cases. 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Kyoto scale of psychological development. Kyoto: Kyoto International Social Welfare Exchange Centre, 1985."},{"key":"2025100510455477000_45.12.802.21","unstructured":"Enjoji M . Enjoji developmental scale. 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