{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T14:31:06Z","timestamp":1792765866810,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T00:00:00Z","timestamp":1720396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100016724","name":"Postgraduate Institute of Medical Education and Research, Chandigarh","doi-asserted-by":"publisher","award":["IM\/78\/01\u201004\u201021\u20100013"],"award-info":[{"award-number":["IM\/78\/01\u201004\u201021\u20100013"]}],"id":[{"id":"10.13039\/100016724","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Iron\u2010refractory iron deficiency anaemia (IRIDA) is a rare autosomal recessive disorder, distinguished by hypochromic microcytic anaemia, low transferrin levels and inappropriately elevated hepcidin (HEPC) levels. It is caused by mutations in <jats:italic>TMPRSS6<\/jats:italic> gene. Systematic screening of 500 pregnant women with iron deficiency anaemia having moderate to severe microcytosis with no other causes of anaemia were enrolled to rule out oral iron refractoriness. It identified a final cohort of 10 (2.15% prevalence) individuals with IRIDA phenotype. Haematological and biochemical analysis revealed significant differences between iron responders and iron non\u2010responders, with iron non\u2010responders showing lower haemoglobin, red blood cell count, serum iron and serum ferritin levels, along with elevated HEPC (9.47\u2009\u00b1\u20092.75\u2009ng\/mL, <jats:italic>p<\/jats:italic>\u2009=\u20090.0009) and erythropoietin (4.58\u2009\u00b1\u20094.07\u2009\u00b5\/mL, <jats:italic>p<\/jats:italic>\u2009=\u20090.0196) levels. Genetic sequencing of the TMPRSS6 gene in this final cohort identified 10 novel variants, including seven missense and three frame\u2010shift mutations, with four missense variants showing high functional impact defining the IRIDA phenotype. Structural analysis revealed significant damage caused by two variants (p.L83R and p.S235R). This study provides valuable insights into IRIDA among pregnant women in the Indian subcontinent, unveiling its underlying causes of unresponsiveness, genetic mechanisms and prevalence. Furthermore, research collaboration is essential to validate these findings and develop effective treatments.<\/jats:p>","DOI":"10.1111\/bjh.19616","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T23:04:59Z","timestamp":1720479899000},"page":"686-698","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel <scp>TMPRSS6<\/scp> variants and their impact on iron\u2010refractory iron deficiency anaemia in pregnancy: A North Indian genotype phenotype study"],"prefix":"10.1111","volume":"205","author":[{"given":"Antika","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Pharmacology Post Graduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Post Graduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kajal","family":"Rawat","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Post Graduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumya","family":"Vij","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Post Graduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arushi","family":"Sandhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Post Graduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vipasha","family":"Gautam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Post Graduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip Kumar","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Post Graduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5925-7159","authenticated-orcid":false,"given":"Lekha","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Post Graduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/2249-4863.141619"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2023.2276851"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2023.147981"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-022-02612-2"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1286058"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409409102"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.130"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-023-05576-w"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3109\/08880018.2016.1157229"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(81)80831-1"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.47046"},{"key":"e_1_2_12_13_1","unstructured":"PFOGSI general clinical practice recommendations management of iron deficiency anemia in pregnancy [Internet]. Available from:https:\/\/www.fogsi.org\/wp\u2010content\/uploads\/2017\/07\/gcpr\u2010recommendation\u2010ida\u201002.pdf"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14554"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg509"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab266"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19669-x"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btl423"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.04.009"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-548"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hemonc.2020.04.007"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.4084\/MJHID.2021.028"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23929"},{"key":"e_1_2_12_26_1","first-page":"475","article-title":"Iron metabolism and iron\u2010refractory iron deficiency anemia","volume":"61","author":"Suzuki T","year":"2020","journal-title":"Jpn J Clin Hematol"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2009.01340.x"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.HS9.0000849084.95795.3d"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2022.146977"},{"key":"e_1_2_12_30_1","first-page":"479","article-title":"Is the acronym IRIDA acceptable for slow responders to iron in the presence of TMPRSS6 mutations?","volume":"55","author":"Yilmaz\u2010Keskin E","year":"2013","journal-title":"Turk J Pediatr"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001640"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21243"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.12395"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-011-0881-0"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13416"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2017.04.002"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.19616","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T06:19:54Z","timestamp":1724739594000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.19616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,8]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1111\/bjh.19616"],"URL":"https:\/\/doi.org\/10.1111\/bjh.19616","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,8]]},"assertion":[{"value":"2024-04-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}