{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:35:57Z","timestamp":1777030557855,"version":"3.51.4"},"reference-count":22,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzen Municipality","doi-asserted-by":"publisher","award":["SZSM202311028"],"award-info":[{"award-number":["SZSM202311028"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Congenital methemoglobinemia caused by hemoglobin variants is a rare hematological disorder often misdiagnosed due to overlapping features with enzymatic defects. Hb T\u00fcbingen, a \u03b2\u2010globin chain variant (\u03b2\n CD106<\/jats:sup>\n ), is characterized by increased autoxidation, heat instability, and cyanosis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A 7\u2010year\u2010old Chinese boy with cyanosis and recurrent neurological symptoms was evaluated using hemoglobin electrophoresis, HPLC, methemoglobin quantification, genetic sequencing, and brain imaging.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Genetic analysis identified the\n HBB<\/jats:italic>\n : c.320\u2009T>A mutation, confirmed by Sanger sequencing. Hemoglobin electrophoresis revealed a false elevation of Hb F (52.3%) due to co\u2010migration of Hb T\u00fcbingen with Hb F, which was validated by HPLC showing normal \u03b3\u2010globin levels. Methemoglobinemia was elevated to 34.4%, accompanied by hemolytic markers (elevated LDH). Brain imaging confirmed Moyamoya disease, a rare cerebrovascular disorder, suggesting potential hypoxia\u2010driven vascular pathology. Family screening revealed autosomal dominant inheritance, with the mutation traced to the patient's mother and maternal relatives.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This study underscores the diagnostic challenges of Hb T\u00fcbingen, particularly its mimicry of Hb F, necessitating further molecular diagnostic approaches. The association with Moyamoya disease highlights unexplored interactions between chronic hypoxia and cerebrovascular remodeling. Our findings expand the genetic epidemiology of Hb T\u00fcbingen and emphasize integrated hematological and neurological evaluations in unexplained cyanosis.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcla.70178","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:52:10Z","timestamp":1775022730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular and Clinical Characterization of the Hb T\u00fcbingen [\u03b2106(\n G8<\/scp>\n ) Leu\u2192\u2009Gln,\n \n HBB<\/i>\n <\/scp>\n : c.\n 320\u2009T<\/scp>\n >A] Associated With Congenital Methemoglobinemia in a Chinese Family"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5171-5474","authenticated-orcid":false,"given":"Hualei","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Laboratory Shenzhen Children's Hospital Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7124-6882","authenticated-orcid":false,"given":"Zhenmin","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Laboratory Shenzhen Children's Hospital Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8037-2175","authenticated-orcid":false,"given":"Yuhua","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, School of Basic Medical Sciences Southern Medical University Guangzhou Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reem Nabil","family":"Hassan","sequence":"additional","affiliation":[{"name":"King Abdul\u2010Aziz University, Faculty of Sciences Biological Sciences Department Jeddah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4210-3510","authenticated-orcid":false,"given":"Xiaoying","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Shenzhen Children's Hospital Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4911-4949","authenticated-orcid":false,"given":"Tao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Shenzhen Children's Hospital Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunsheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Shenzhen Children's Hospital Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4689-0966","authenticated-orcid":false,"given":"Xufeng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Neurology Shenzhen Children's Hospital, China Medical University Shenyang Liaoning China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"issue":"7","key":"e_1_2_11_2_1","article-title":"Congenital Methemoglobinemia and Unstable Hemoglobin Variant in a Child With Cyanosis","volume":"13","author":"Alsabri 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