{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T19:53:43Z","timestamp":1769198023101,"version":"3.49.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"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. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study was conducted to investigate the clinical and genetic characteristics of a family affected by hereditary spherocytosis (HS) combined with familial chylomicronemia syndrome (FCS), identify the pathogenic cause, and provide a basis for the clinical diagnosis, treatment, and genetic counseling of affected children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical data were collected from family members. High-throughput sequencing was performed to identify pathogenic variants in genes associated with HS and FCS in the proband. Suspected pathogenic mutations were confirmed in family members via PCR-Sanger sequencing. Bioinformatics analysis and three-dimensional protein structure prediction were also conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The proband presented with severe anemia, splenomegaly, and jaundice. Genetic testing revealed a heterozygous mutation, c.6005G&amp;gt;A (p.Trp2002*), in the spectrin beta chain (\n                      <jats:italic>SPTB<\/jats:italic>\n                      )gene (NM_001355436.2) and a missense mutation, c.292G&amp;gt;A (p.Ala98Thr), in the lipoprotein lipase (\n                      <jats:italic>LPL<\/jats:italic>\n                      ) gene (NM_000237.3). The\n                      <jats:italic>SPTB<\/jats:italic>\n                      c.6005G&amp;gt;A (p.Trp2002*) mutation was inherited from the mother, who exhibited mild anemia, jaundice, and splenomegaly. The\n                      <jats:italic>LPL<\/jats:italic>\n                      c.292G&amp;gt;A (p.Ala98Thr) mutation was inherited from the father, who had hypertriglyceridemia. The\n                      <jats:italic>SPTB<\/jats:italic>\n                      c.6005G&amp;gt;A (p.Trp2002*) mutation is extremely rare in the general population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The heterozygous mutations\n                      <jats:italic>SPTB<\/jats:italic>\n                      c.6005G&amp;gt;A (p.Trp2002*) and\n                      <jats:italic>LPL<\/jats:italic>\n                      c.292G&amp;gt;A (p.Ala98Thr) are the pathogenic causes in this family and provide a basis for clinical management and genetic counseling. Based on the HGMD, 1000G, and ExAC databases, the\n                      <jats:italic>SPTB<\/jats:italic>\n                      c.6005G&amp;gt;A (p.Trp2002*) mutation is reported here for the first time, enriching the mutation spectrum of the\n                      <jats:italic>SPTB<\/jats:italic>\n                      gene.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1659838","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T22:10:27Z","timestamp":1769119827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Clinical and genetic analysis of a family with hereditary spherocytosis combined with familial chylomicronemia syndrome"],"prefix":"10.3389","volume":"17","author":[{"given":"Yumei","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Precision Medicine for Viral Diseases, Guangxi Health Commission Key Laboratory of Clinical Biotechnology, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Precision Medicine for Viral Diseases, Guangxi Health Commission Key Laboratory of Clinical Biotechnology, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kecheng","family":"Li","sequence":"additional","affiliation":[{"name":"Blood Transfusion Department, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaoming","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Precision Medicine for Viral Diseases, Guangxi Health Commission Key Laboratory of Clinical Biotechnology, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hualian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Precision Medicine for Viral Diseases, Guangxi Health Commission Key Laboratory of Clinical Biotechnology, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Precision Medicine for Viral Diseases, Guangxi Health Commission Key Laboratory of Clinical Biotechnology, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Precision Medicine for Viral Diseases, Guangxi Health Commission Key Laboratory of Clinical Biotechnology, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Precision Medicine for Viral Diseases, Guangxi Health Commission Key Laboratory of Clinical Biotechnology, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyue","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Precision Medicine for Viral Diseases, Guangxi Health Commission Key Laboratory of Clinical Biotechnology, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingjiang","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shifu","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Key Laboratory of Precision Medicine for Viral Diseases, Guangxi Health Commission Key Laboratory of Clinical Biotechnology, Liuzhou People\u2019s Hospital","place":["Liuzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3923\/pjbs.2010.73.77","article-title":"Biochemical changes of hemoglobin and osmotic fragility of red blood cells in high fat diet rabbits","volume":"13","author":"Abdelhalim","year":"2010","journal-title":"Pak J. Biol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.21037\/tp-22-515","article-title":"Familial chylomicronemia syndrome in children: a diagnosis challenge","volume":"11","author":"Ariza","year":"2022","journal-title":"Transl. Pediatr."},{"key":"B3","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1016\/j.arteri.2024.11.001","article-title":"Genetic basis of hypertriglyceridemia","volume":"36","author":"Ariza Corbo","year":"2024","journal-title":"Clin. Investig. Arterioscler."},{"key":"B4","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/joim.13016","article-title":"Familial chylomicronemia syndrome: an under-recognized cause of severe hypertriglyceridaemia","volume":"287","author":"Baass","year":"2020","journal-title":"J. Intern Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/vcp.12155","article-title":"Increases in beta-lipoproteins in hyperlipidemic and dyslipidemic dogs are associated with increased erythrocyte osmotic fragility","volume":"43","author":"Behling-Kelly","year":"2014","journal-title":"Vet. Clin. Pathol."},{"key":"B6","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--2011 update","volume":"156","author":"Bolton-Maggs","year":"2012","journal-title":"Br. J. Haematol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"119114","DOI":"10.1016\/j.atherosclerosis.2025.119114","article-title":"Familial chylomicronemia syndrome and treatments to target hepatic APOC3 mRNA","volume":"403","author":"Brinton","year":"2025","journal-title":"Atherosclerosis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e0483","DOI":"10.1097\/MD.0000000000010483","article-title":"The HindIII and PvuII polymorphisms of lipoprotein lipase (LPL) gene reduce the risk of ischemic stroke (IS): a meta-analysis","volume":"97","author":"Cao","year":"2018","journal-title":"Med. Baltim."},{"key":"B9","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/humu.9054","article-title":"Genotype-phenotype studies of six novel LPL mutations in Chinese patients with hypertriglyceridemia","volume":"20","author":"Chan","year":"2002","journal-title":"Hum. Mutat."},{"key":"B10","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/1476-511X-13-52","article-title":"A novel lipoprotein lipase gene missense mutation in Chinese patients with severe hypertriglyceridemia and pancreatitis","volume":"13","author":"Chen","year":"2014","journal-title":"Lipids Health Dis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.tcm.2019.03.001","article-title":"Familial chylomicronemia syndrome: a rare but devastating autosomal recessive disorder characterized by refractory hypertriglyceridemia and recurrent pancreatitis","volume":"30","author":"Chyzhyk","year":"2020","journal-title":"Trends Cardiovasc Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s11883-020-00885-1","article-title":"Familial chylomicronemia syndrome (FCS): recent data on diagnosis and treatment","volume":"22","author":"Gallo","year":"2020","journal-title":"Curr. Atheroscler. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/s0003-3995(01)01037-1","article-title":"Lipoprotein lipase (LPL) deficiency: a new patient homozygote for the preponderant mutation Gly188Glu in the human LPL gene and review of reported mutations: 75 % are clustered in exons 5 and 6","volume":"44","author":"Gilbert","year":"2001","journal-title":"Ann. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.cca.2022.10.001","article-title":"Familial chylomicronemia syndrome caused by compound heterozygous mutation of lipoprotein lipase gene: a case report and review of literature","volume":"537","author":"Huang","year":"2022","journal-title":"Clin. Chim. Acta"},{"key":"B15","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.jacl.2018.03.021","article-title":"Prevalence of familial chylomicronemia syndrome (FCS): are we underestimating?","volume":"12","author":"Khavandi","year":"2018","journal-title":"J. Clin. Lipidol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s00439-025-02748-8","article-title":"Understanding the genetic architecture and phenotypic landscape of SPTBgene variants causing hereditary spherocytosis in an Indian cohort","volume":"144","author":"More","year":"2025","journal-title":"Hum. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2276","DOI":"10.1177\/2047487319888054","article-title":"Prevalence of familial chylomicronemia syndrome in a Quaternary care center","volume":"27","author":"Pallazola","year":"2020","journal-title":"Eur. J. Prev. Cardiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"27362","DOI":"10.1038\/s41598-024-78622-w","article-title":"Identification and functional analysis of novel SPTBand ANK1 mutations in hereditary spherocytosis patients","volume":"14","author":"Panarach","year":"2024","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1016\/S0140-6736(08)61588-3","article-title":"Hereditary spherocytosis","volume":"372","author":"Perrotta","year":"2008","journal-title":"Lancet"},{"key":"B20","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1111\/ijlh.14376","article-title":"Overview on hereditary spherocytosis diagnosis","volume":"47","author":"Polizzi","year":"2025","journal-title":"Int. J. Lab. Hematol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/j.jacc.2018.06.042","article-title":"Familial chylomicronemia syndrome: clinical characteristics and long-term cardiovascular outcomes","volume":"72","author":"Shah","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1056\/NEJMoa2400201","article-title":"Olezarsen, acute pancreatitis, and familial chylomicronemia syndrome","volume":"390","author":"Stroes","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1080\/16078454.2019.1650873","article-title":"Targeted next-generation sequencing identified a novel ANK1 mutation associated with hereditary spherocytosis in a Chinese family","volume":"24","author":"Sun","year":"2019","journal-title":"Hematology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1111\/bjh.16750","article-title":"Genotype-phenotype correlation in children with hereditary spherocytosis","volume":"191","author":"Tole","year":"2020","journal-title":"Br. J. Haematol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1497588","DOI":"10.3389\/fphys.2025.1497588","article-title":"An overview of hereditary spherocytosis and the curative effects of splenectomy","volume":"16","author":"Turpaev","year":"2025","journal-title":"Front. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12920-024-01973-w","article-title":"A novel variant in the SPTBgene underlying hereditary spherocytosis and a literature review of previous variants","volume":"17","author":"Wang","year":"2024","journal-title":"BMC Med. Genomics"},{"key":"B27","first-page":"84","article-title":"Chylomicronemia syndrome complicating type 1 hyperlipoproteinemia with concomitant insulin-dependent diabetes","volume":"6","author":"Wojtukiewicz","year":"1999","journal-title":"Pol. Merkur Lek."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e24034","DOI":"10.1002\/jcla.24034","article-title":"The diagnostic protocol for hereditary spherocytosis-2021 update","volume":"35","author":"Wu","year":"2021","journal-title":"J. Clin. Lab. Anal."},{"key":"B29","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1186\/s13023-024-03290-y","article-title":"Clinical and genetic characteristics of Chinese pediatric and adult patients with hereditary spherocytosis","volume":"19","author":"Wu","year":"2024","journal-title":"Orphanet J. Rare Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e0129488","DOI":"10.1371\/journal.pone.0129488","article-title":"Genetic variants associated with gestational hypertriglyceridemia and pancreatitis","volume":"10","author":"Xie","year":"2015","journal-title":"PLoS One"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1659838\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T22:10:40Z","timestamp":1769119840000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1659838\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":30,"alternative-id":["10.3389\/fgene.2026.1659838"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1659838","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]},"article-number":"1659838"}}