{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T07:02:26Z","timestamp":1780038146468,"version":"3.53.1"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hereditary spherocytosis (HS) is an inherited form of hemolytic anemia resulting from defects in the red blood cell membrane skeleton. Its classic clinical presentation includes anemia, jaundice, and splenomegaly. Key laboratory findings that support the diagnosis are the presence of spherocytes and an elevated reticulocyte count on peripheral blood smear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      An 8-year-old girl presented with a longstanding history of jaundice\u2014noted for four years\u2014affecting both her skin and sclera. She also reported intermittent episodes of tea-colored urine. Physical examination revealed hepatosplenomegaly. Laboratory investigations demonstrated normocytic anemia, a positive osmotic fragility test, and the presence of spherocytes on peripheral blood smear, which was subsequently confirmed by electron microscopy. Whole-exome sequencing identified a novel heterozygous pathogenic mutation (c.2388\u2009+\u20092T\u2009&amp;gt;\u2009A) in the\n                      <jats:italic>ANK1<\/jats:italic>\n                      gene (NM_000037.4, Intron). This splice-site mutation leads to aberrant splicing, causing a frameshift and introduction of a premature termination codon (PTC), likely triggering nonsense-mediated mRNA decay (NMD) and resulting in a truncated, dysfunctional Ankyrin-1 protein.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study reports a novel\n                      <jats:italic>ANK1<\/jats:italic>\n                      mutation (c.2388\u2009+\u20092T\u2009&amp;gt;\u2009A) identified in a Chinese patient with hereditary spherocytosis. Located at a critical splice donor site, this previously unreported variant is predicted to cause disease through the inclusion of a cryptic exon. The finding provides new insight into the genetic basis of HS in the Chinese population.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1760131","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:10:58Z","timestamp":1780035058000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel ANK1 gene mutation associated with hereditary spherocytosis: a case report"],"prefix":"10.3389","volume":"14","author":[{"given":"Mingqian","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]},{"name":"Department of Pediatrics, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]},{"name":"Maternal and Child Research Institute, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengqiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Maternal and Child Research Institute, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]},{"name":"Maternal and Child Research Institute, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronghua","family":"Pan","sequence":"additional","affiliation":[{"name":"Maternal and Child Research Institute, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijun","family":"Huang","sequence":"additional","affiliation":[{"name":"Maternal and Child Research Institute, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Maternal and Child Research Institute, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoda","family":"Ma","sequence":"additional","affiliation":[{"name":"Maternal and Child Research Institute, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology and Oncology, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]},{"name":"Department of Pediatrics, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]},{"name":"Maternal and Child Research Institute, Shunde Women and Children\u2019s Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan), Guangdong Medical University","place":["Foshan, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1007\/s11427-017-9232-6","article-title":"Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis","volume":"61","author":"Wang","year":"2018","journal-title":"Sci China Life Sci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"76","DOI":"10.5582\/irdr.2015.01002","article-title":"A systematic review of hereditary spherocytosis reported in Chinese biomedical journals from 1978 to 2013 and estimation of the prevalence of the disease using a disease model","volume":"4","author":"Wang","year":"2015","journal-title":"Intractable Rare Dis Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1159\/000486229","article-title":"Molecular genetic mechanisms of hereditary spherocytosis: current perspectives","volume":"139","author":"He","year":"2018","journal-title":"Acta Haematol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3389\/fgene.2023.1088985","article-title":"Clinical manifestations of 17 Chinese children with hereditary spherocytosis caused by novel mutations of the ANK1 gene and phenotypic analysis","author":"Kang","year":"2023","journal-title":"Front Genet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1111\/j.1365-2141.2011.08921.x","article-title":"Guidelines for the diagnosis and management of hereditary spherocytosis\u20142011 update","volume":"156","author":"Bolton-Maggs","year":"2012","journal-title":"Br J Haematol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.652376","article-title":"Preliminary study on the clinical and genetic characteristics of hereditary spherocytosis in 15 Chinese children","volume":"12","author":"Wu","year":"2021","journal-title":"Front Genet"},{"key":"B7","doi-asserted-by":"publisher","first-page":"565","DOI":"10.11817\/j.issn.1672-7347.2023.220390","article-title":"Clinical and genetic diagnosis for 26 paitents with hereditary spherocytosis","volume":"48","author":"Bai","year":"2023","journal-title":"Journal of Central South University (Medical Sciences)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"898","DOI":"10.3760\/cma.j.issn.0253-2727.2018.11.005","article-title":"The characteristic of hereditary spherocytosis related gene mutation in 37 Chinese hereditary spherocytisis patients","volume":"39","author":"Peng","year":"2018","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"B9","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1111\/bjh.16244","article-title":"Deciphering molecular heterogeneity of Indian families with hereditary spherocytosis using targeted next-generation sequencing: first South Asian study","volume":"188","author":"Aggarwal","year":"2020","journal-title":"Br J Haematol"},{"key":"B10","first-page":"1093","volume-title":"Deep Intronic Mutations and Human Disease. Human Genetics","author":"Vaz-Drago","year":"2017"},{"key":"B11","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1038\/s41594-022-00792-w","article-title":"Architecture of the human erythrocyte ankyrin-1 complex","volume":"29","author":"Vallese","year":"2022","journal-title":"Nat Struct Mol Biol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"4093","DOI":"10.1182\/blood-2009-11-255604","article-title":"Structural basis for spectrin recognition by ankyrin","volume":"115","author":"Ipsaro","year":"2010","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s12887-022-03795-0","article-title":"De novo variations of ANK1 gene caused hereditary spherocytosis in two Chinese children by affecting pre-mRNA splicing","volume":"23","author":"Wang","year":"2023","journal-title":"BMC Pediatr"},{"key":"B14","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/cge.12749","article-title":"Mutational characteristics of ANK1 and SPTB genes in hereditary spherocytosis","volume":"90","author":"Park","year":"2016","journal-title":"Clin Genet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00953","article-title":"Genetic and clinical characteristics of patients with hereditary spherocytosis in Hubei province of China","volume":"11","author":"Wang","year":"2020","journal-title":"Front Genet"},{"key":"B16","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12920-024-01973-w","article-title":"A novel variant in the SPTB gene underlying hereditary spherocytosis and a literature review of previous variants","volume":"17","author":"Wang","year":"2024","journal-title":"BMC Med Genomics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1093\/micmic\/ozac055","article-title":"Membrane protein detection and morphological analysis of red blood cells in hereditary spherocytosis by confocal Laser scanning microscopy","volume":"29","author":"Rey-Barroso","year":"2023","journal-title":"Microsc Microanal"},{"key":"B18","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/j.gene.2017.07.009","article-title":"Novel mutations in patients with hereditary red blood cell membrane disorders using next-generation sequencing","volume":"627","author":"He","year":"2017","journal-title":"Gene"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1760131\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:11:01Z","timestamp":1780035061000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1760131\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":18,"alternative-id":["10.3389\/fped.2026.1760131"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1760131","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1760131"}}