{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T16:41:44Z","timestamp":1775839304232,"version":"3.50.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital sideroblastic anemia (CSA) constitutes a group of inherited erythropoietic disorders. Some affect mainly or exclusively erythroid cells; other syndromic forms occur within multisystem disorders with extensive nonhematopoietic manifestations. In this study, we have performed clinical and molecular investigations on a 10-year-old boy suspected of having CSA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Routine blood examination, peripheral blood and bone marrow smears, and serum iron tests were performed. Gene mutation analysis was conducted using whole-exome sequencing (WES) and the results were confirmed using Sanger sequencing. Furthermore, the functional impact of the identified variant was assessed\/predicted with bioinformatics methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient presented with severe microcytic anemia (hemoglobin, 50\u2005g\/L), iron overload and ring sideroblasts in the bone marrow. Moreover, WES revealed the presence of a hemizygous missense variant in <jats:italic>ALAS2<\/jats:italic> (c.1102C\u2009&amp;gt;\u2009T), changing an encoded arginine to tryptophan (p. Arg368Trp). This variant was verified via Sanger sequencing, and neither of the parents carried this variant, which was suspected to be a <jats:italic>de novo<\/jats:italic> variant. Using <jats:italic>in silico<\/jats:italic> analysis with four different software programs, the variant was predicted to be harmful. PyMol and LigPlot software showed that the p. Arg368Trp variant may result in changes in hydrogen bonds. The patient was treated with vitamin B6 combined with deferasirox. After 6 months, the hemoglobin increased to 99\u2005g\/L and the serum ferritin decreased significantly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We report a novel pathogenic variant in the <jats:italic>ALAS2<\/jats:italic> gene (c.1102C\u2009&amp;gt;\u2009T:p. Arg368Trp), which caused CSA in a 10-year-old boy. Mutational analysis is important in patients with CSA when family history data are unavailable. Anemia due to the <jats:italic>ALAS2<\/jats:italic> Arg368Trp variant responds to pyridoxine supplements.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2024.1411676","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T04:59:36Z","timestamp":1724907576000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel and apparent de novo ALAS2 missense variant associated with congenital sideroblastic anemia"],"prefix":"10.3389","volume":"12","author":[{"given":"Jianling","family":"Cai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meidie","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanqin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.hoc.2014.04.008","article-title":"Sideroblastic anemia: diagnosis and management","volume":"28","author":"Bottomley","year":"2014","journal-title":"Hematol Oncol Clin North Am"},{"key":"B2","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1182\/blood-2018-08-815951","article-title":"The molecular genetics of sideroblastic anemia","volume":"133","author":"Ducamp","year":"2019","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/genes13091562","article-title":"Causes and pathophysiology of acquired sideroblastic anemia","volume":"13","author":"Rodriguez-Sevilla","year":"2022","journal-title":"Genes (Basel)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/j.gene.2018.05.074","article-title":"Congenital sideroblastic anemia: advances in gene mutations and pathophysiology","volume":"668","author":"Long","year":"2018","journal-title":"Gene"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1002\/humu.24267","article-title":"SLC25A38 Congenital sideroblastic anemia: phenotypes and genotypes of 31 individuals from 24 families, including 11 novel mutations, and a review of the literature","volume":"42","author":"Heeney","year":"2021","journal-title":"Hum Mutat"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3202","DOI":"10.3324\/haematol.2021.279138","article-title":"Biallelic mutations in the SARS2 gene presenting as congenital sideroblastic anemia","volume":"106","author":"Colin","year":"2021","journal-title":"Haematologica"},{"key":"B7","doi-asserted-by":"publisher","first-page":"692459","DOI":"10.3389\/fped.2021.692459","article-title":"The first case report of X-linked sideroblastic anemia with ataxia of Chinese origin and literature review","volume":"9","author":"Xiong","year":"2021","journal-title":"Front Pediatr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the association for molecular pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"D377","DOI":"10.1093\/nar\/gks1118","article-title":"PANTHER In 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees","volume":"41","author":"Mi","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/0888-7543(92)90223-f","article-title":"Assignment of human erythroid delta-aminolevulinate synthase (ALAS2) to a distal subregion of band Xp11.21 by PCR analysis of somatic cell hybrids containing X; autosome translocations","volume":"13","author":"Cotter","year":"1992","journal-title":"Genomics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s00277-019-03894-6","article-title":"Identification of a novel heterozygous ALAS2 mutation in a young Chinese female with X-linked sideroblastic anemia","volume":"99","author":"Qiu","year":"2020","journal-title":"Ann Hematol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1186\/s12920-021-01146-z","article-title":"X-linked sideroblastic anaemia in a female fetus: a case report and a literature review","volume":"14","author":"Nzelu","year":"2021","journal-title":"BMC Med Genomics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.7499\/j.issn.1008-8830.2019.10.012","article-title":"[Clinical features and gene mutation spectrum in children with sideroblastic anemia]","volume":"21","author":"An","year":"2019","journal-title":"Zhongguo Dang Dai Er Ke Za Zhi"},{"key":"B14","year":"2023"},{"key":"B15","doi-asserted-by":"crossref","first-page":"3915","DOI":"10.1182\/blood.V84.11.3915.bloodjournal84113915","article-title":"X-linked sideroblastic anemia: identification of the mutation in the erythroid-specific delta-aminolevulinate synthase gene (ALAS2) in the original family described by cooley","volume":"84","author":"Cotter","year":"1994","journal-title":"Blood"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2813","DOI":"10.1038\/s41467-020-16586-x","article-title":"Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release","volume":"11","author":"Bailey","year":"2020","journal-title":"Nat Commun"},{"key":"B17","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/s1570-9639(03)00095-5","article-title":"5-Aminolevulinic Acid synthase: mechanism, mutations and medicine","volume":"1647","author":"Shoolingin-Jordan","year":"2003","journal-title":"Biochim Biophys Acta"},{"key":"B18","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1002\/mgg3.202","article-title":"Sideroblastic anemia: functional study of two novel missense mutations in ALAS2","volume":"4","author":"M\u00e9ndez","year":"2016","journal-title":"Mol Genet Genomic Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"101643","DOI":"10.1016\/j.jbc.2022.101643","article-title":"Structural basis for dysregulation of aminolevulinic acid synthase in human disease","volume":"298","author":"Taylor","year":"2022","journal-title":"J Biol Chem"},{"key":"B20","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s12185-017-2368-0","article-title":"Iron metabolism in erythroid cells and patients with congenital sideroblastic anemia","volume":"107","author":"Furuyama","year":"2018","journal-title":"Int J Hematol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"9024","DOI":"10.1038\/s41598-022-12940-9","article-title":"Congenital sideroblastic anemia model due to ALAS2 mutation is susceptible to ferroptosis","volume":"12","author":"Ono","year":"2022","journal-title":"Sci Rep"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1009988","DOI":"10.3389\/fgene.2022.1009988","article-title":"Case report: an infant boy with X-linked sideroblastic anaemia successfully treated by umbilical cord blood haematopoietic stem cell transplantation","volume":"13","author":"Ma","year":"2022","journal-title":"Front Genet"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1182\/bloodadvances.2020002177","article-title":"Development of luspatercept to treat ineffective erythropoiesis","volume":"5","author":"Kubasch","year":"2021","journal-title":"Blood Adv"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1038\/s41375-022-01521-4","article-title":"Luspatercept for myelodysplastic syndromes\/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis","volume":"36","author":"Komrokji","year":"2022","journal-title":"Leukemia"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1056\/NEJMc2216213","article-title":"Luspatercept as potential treatment for congenital sideroblastic Anemia","volume":"388","author":"Van Dijck","year":"2023","journal-title":"N Engl J Med"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2024.1411676\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T04:59:39Z","timestamp":1724907579000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2024.1411676\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,29]]},"references-count":25,"alternative-id":["10.3389\/fped.2024.1411676"],"URL":"https:\/\/doi.org\/10.3389\/fped.2024.1411676","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,29]]},"article-number":"1411676"}}