{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:58:32Z","timestamp":1788875912110,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T00:00:00Z","timestamp":1695513600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Synonymous mutations were considered to lack functional roles in human diseases; however, distinguishing deleterious synonymous mutations from benign ones is still a challenge. In this article, we identified a deleterious synonymous mutation \u03b2\u2010codon 16 (C&gt;T). <jats:italic>HBB<\/jats:italic>: c.51C&gt;T, in compound heterozygous form with known \u03b2\u2010thalassaemia mutation patients who clinically presented as non\u2010transfusion\u2010dependent thalassaemia (NTDT). A total of 9 families with 11 compound heterozygous index cases were reported. In the heterozygous state, codon 16 (C&gt;T) mutation results in borderline HbA<jats:sub>2<\/jats:sub> (3.18\u2009\u00b1\u20090.36%) and slightly reduced RBC indices (RBCs: 4.73\u2009\u00b1\u20090.75\u2009\u00d7\u200910<jats:sup>6<\/jats:sup>\/\u03bcL, Hb: 12.26\u2009\u00b1\u20092.60\u2009g\/dL, MCV: 79.48\u2009\u00b1\u20098.40\u2009fL, MCH: 25.95\u2009\u00b1\u20094.15\u2009pg). The compound heterozygous patients showed elevated HbA<jats:sub>2<\/jats:sub> (5.98\u2009\u00b1\u20091.17%) and HbF (12.75\u2009\u00b1\u20097.51%) and presented clinically as NTDT with a mean Hb of 6.95\u2009\u00b1\u20091.29\u2009g\/dL. Many of them were dependent on few transfusions and had mild splenomegaly. Of the 11 patients, 5 (45.4%) were treated with hydroxyurea. This study highlights the clinical significance of synonymous mutation, when inherited with other \u03b2\u2010thalassaemia mutations leading to the phenotype of NTDT. Thus, the study would help to improve screening protocols for \u03b2\u2010thalassaemia carriers, which will ultimately improve the prevention programme.<\/jats:p>","DOI":"10.1111\/bjh.19115","type":"journal-article","created":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T23:10:11Z","timestamp":1695597011000},"page":"677-682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["When a synonymous mutation breaks the silence in a thalassaemia patient"],"prefix":"10.1111","volume":"204","author":[{"given":"M.","family":"Gorivale","sequence":"first","affiliation":[{"name":"ICMR\u2010National Institute of Immunohaematology  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Sawant","sequence":"additional","affiliation":[{"name":"ICMR\u2010National Institute of Immunohaematology  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Kargutkar","sequence":"additional","affiliation":[{"name":"ICMR\u2010National Institute of Immunohaematology  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Hariharan","sequence":"additional","affiliation":[{"name":"ICMR\u2010National Institute of Immunohaematology  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Thaker","sequence":"additional","affiliation":[{"name":"ICMR\u2010National Institute of Immunohaematology  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Chiddarwar","sequence":"additional","affiliation":[{"name":"ICMR\u2010National Institute of Immunohaematology  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6039-924X","authenticated-orcid":false,"given":"A.","family":"Nadkarni","sequence":"additional","affiliation":[{"name":"ICMR\u2010National Institute of Immunohaematology  Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,9,24]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3051"},{"issue":"3","key":"e_1_2_12_3_1","first-page":"576","article-title":"Localization of the beta\u2010globin gene by chromosomal in situ hybridization","volume":"36","author":"Morton CC","year":"1984","journal-title":"Am J Hum Genet"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2017.06.001"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181cd68ed"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phoj.2017.10.002"},{"key":"e_1_2_12_7_1","unstructured":"HbVar: a database of human hemoglobin variants and thalassemias. [cited 2023 Mar 28]. Available from:http:\/\/globin.cse.psu.edu\/globin\/hbvar"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/03630260802626012"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCP70ORBRURVSJM"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881\u2010019\u20100926\u20104"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013574"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg055"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.8.2318"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174637"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V69.4.1141.1141"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.19746\/j.cnki.issn.1009\u20102137.2020.02.037"},{"issue":"4","key":"e_1_2_12_17_1","first-page":"164","article-title":"Identification of a rare synonymous Beta globin mutation, HBB:c.180G>a codon 59 (G>a) in an Iranian patient","volume":"1","author":"Akhavan\u2010Niaki H","year":"2015","journal-title":"IBBJ Autumn"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12433"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/300768a0"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.19115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T06:04:48Z","timestamp":1707285888000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.19115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,24]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1111\/bjh.19115"],"URL":"https:\/\/doi.org\/10.1111\/bjh.19115","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,24]]},"assertion":[{"value":"2023-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}