{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T09:49:21Z","timestamp":1791798561477,"version":"4.3.4"},"reference-count":18,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:00:00Z","timestamp":1791763200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To report two cases of hemoglobin H (HbH) disease with routine genetic testing missed rare variants, where the phenotype was inconsistent with routine genetic testing results, explore their true genotypes and clinical characteristics, and evaluate the application value of single\u2010molecule nanopore sequencing (CycloneSEQ platform) in detecting rare thalassemia variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Common thalassemia gene testing was performed on two adult male patients who presented with different complications. The results showed \u2010\u2010\n                      <jats:sup>SEA<\/jats:sup>\n                      \/\u03b1\u03b1, which was significantly inconsistent with their hematological parameters. Subsequently, long\u2010read sequencing of the \u03b1\u2010globin gene cluster was conducted using the CycloneSEQ platform (single\u2010molecule nanopore sequencing technology), and specific primers were designed based on the results for PCR verification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The two patients were ultimately diagnosed with rare deletional HbH disease with the genotype\n                      <jats:italic>\u2010\u2010<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>SEA<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>\/\u2010\u03b1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>4.3<\/jats:italic>\n                      <\/jats:sup>\n                      (NC_000016.10:g.176935\u2010181274DEL). The deletion range includes the \u03b11 gene and is accompanied by an X\u2010Y\u2010Z segment recombination, which is reported here for the first time. Both patients exhibited varying degrees of anemia and complications, suggesting that the same genotype can manifest significant phenotypic heterogeneity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Conventional thalassemia testing fails to identify rare deletional HbH disease, frequently causing genotype\u2013phenotype discordance and diagnostic bias. The newly reported\n                      <jats:italic>\u2010\u2010<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>SEA<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>\/\u2010\u03b1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>4.3<\/jats:italic>\n                      <\/jats:sup>\n                      genotype with X\u2010Y\u2010Z recombination expands the HbH disease genotypic spectrum and confirms obvious phenotypic heterogeneity. CycloneSEQ nanopore sequencing effectively detects rare complex variants undetectable by routine methods, supporting precise diagnosis of atypical thalassemia with favorable clinical prospects.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcla.70379","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T09:26:57Z","timestamp":1791797217000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phenotypic and Genotypic Analysis of Two Rare Cases of \u2010\u2010\n                    <scp>\n                      <sup>SEA<\/sup>\n                    <\/scp>\n                    \/\u2010\u03b1\n                    <sup>4.3<\/sup>\n                    <scp>HbH<\/scp>\n                    Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5078-7353","authenticated-orcid":false,"given":"Weijia","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Eugenics and Genetics Guilin People's Hospital  Guilin Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Huang","sequence":"additional","affiliation":[{"name":"BGI Genomics co., Ltd.  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Guilin People's Hospital  Guilin Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7237-6807","authenticated-orcid":false,"given":"Xiaoqin","family":"Yang","sequence":"additional","affiliation":[{"name":"BGI Genomics co., Ltd.  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaya","family":"Guo","sequence":"additional","affiliation":[{"name":"BGI Genomics co., Ltd.  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingping","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Eugenics and Genetics Guilin People's Hospital  Guilin Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9302-8018","authenticated-orcid":false,"given":"Min","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Eugenics and Genetics Guilin People's Hospital  Guilin Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guijun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiology Guilin People's Hospital  Guilin Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101165"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/03630269.2021.2008960"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.62347\/CQDH5278"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/10760296221119807"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn231583\u201020230104\u201000002"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.0253\u20109802.2020.12.010"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1003\u20106350.2019.10.008"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1003\u20101383.2019.05.004"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.19829\/zgfybj.issn.1001\u20104411.2019.21.055"},{"key":"e_1_2_13_11_1","volume-title":"StatPearls","author":"Harewood J.","year":"2025"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27440"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010020\u201001429\u20101"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1695120"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2022.12.004"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/17474086.2020.1803736"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25046"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jha2.70087"},{"key":"e_1_2_13_19_1","unstructured":"Y.Liu \u201cA Cohort Study on the Heterogeneity of 591 Patients With HbH Disease [Doctoral Thesis] \u201dSouthern Medical University Guangzhou (2025) Available from CNKI."}],"container-title":["Journal of Clinical Laboratory Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.70379","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcla.70379","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.70379","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T09:27:04Z","timestamp":1791797224000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcla.70379"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,12]]},"references-count":18,"alternative-id":["10.1002\/jcla.70379"],"URL":"https:\/\/doi.org\/10.1002\/jcla.70379","archive":["Portico"],"relation":{},"ISSN":["0887-8013","1098-2825"],"issn-type":[{"value":"0887-8013","type":"print"},{"value":"1098-2825","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,12]]},"assertion":[{"value":"2026-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70379"}}