{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T04:03:23Z","timestamp":1770437003608,"version":"3.49.0"},"reference-count":11,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Haematol"],"abstract":"<b><i>Introduction:<\/i><\/b> Recessive congenital methemoglobinemia (RCM) caused by CYB5R3 deficiency due to the mutations in the reduced nicotinamide adenine dinucleotide (NADH) cytochrome b5 reductase (<i>CYB5R<\/i>) gene is an autosomal recessive inherited disease. Clinically, it can be divided into two types, namely red blood cell affected type (RCM I) and systemically affected type (RCM II). <b><i>Case Presentation:<\/i><\/b> A 5-year-old male patient was diagnosed with cyanosis for 5 years. Physical examination showed cyanosis in areas such as the lips, fingers, and toes. Laboratory examination revealed low pulse oxygen saturation (81%) and increased blood methemoglobin (23.6%). Gene testing revealed the compound heterozygous mutations in the <i>CYB5R3<\/i> gene, c.149G&gt;A (p.Arg50Gln) and c.331A&gt;G (p.Lys111Glu), respectively originating from his parents. By constructing 3D models of <i>CYB5R3<\/i> wild-type and mutant types using SWISS-MODEL software, it was found that the mutation caused significant structural abnormalities in the CYB5R protein. The relationship between <i>CYB5R3<\/i> gene mutation sites, amino acid change, enzyme activity, and methemoglobinemia type I and II were listed and analyzed. <b><i>Conclusion:<\/i><\/b> A case of congenital RCM type I caused by compound heterozygous mutations in the <i>CYB5R3<\/i> gene was reported, with c.331A&gt;G (p.Lys111Glu) being the newly reported mutation. The homozygosity or heterozygosity of <i>CYB5R3<\/i> gene mutations that lead to premature termination, loss of exons, and change in amino acid properties in FAD or NADH binding domains, is positively correlated with the severity (from type I to type II) of methemoglobinemia. <\/jats:p>","DOI":"10.1159\/000539448","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T21:00:26Z","timestamp":1716843626000},"page":"1-7","source":"Crossref","is-referenced-by-count":1,"title":["Novel Compound Heterogeneous Mutations in <i>CYB5R3<\/i> Gene Leading to Methemoglobinemia (Type I) in a Chinese Boy: Case Report and Relevant Comprehensive Analysis"],"prefix":"10.1159","author":[{"given":"Yeyi","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yezhen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Meng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lihua","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuocheng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.31"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2018-2814"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1177\/0883073813512026"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm337"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23973"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12326"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v97.4.1106"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v97.4.1106"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.3390\/medicina59020379"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000705"}],"container-title":["Acta Haematologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/aha\/article-pdf\/doi\/10.1159\/000539448\/4247607\/000539448.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/aha\/article-pdf\/doi\/10.1159\/000539448\/4247607\/000539448.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:22:40Z","timestamp":1745421760000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000539448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,24]]},"references-count":11,"URL":"https:\/\/doi.org\/10.1159\/000539448","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.25886185","asserted-by":"subject"}]},"ISSN":["0001-5792","1421-9662"],"issn-type":[{"value":"0001-5792","type":"print"},{"value":"1421-9662","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,24]]}}}