{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:17:24Z","timestamp":1788283044624,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,11]],"date-time":"2024-02-11T00:00:00Z","timestamp":1707609600000},"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":["Haemophilia"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Various risk factors for inhibitor development in haemophilia A (HA) have been described but Indian data remains scanty.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>We aimed to evaluate the genetic changes in Indian HA\u2010patients that are associated with the development of inhibitors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>All HA\u2010patients with inhibitors who availed coagulation\u2010laboratory services from January\u20102015 till December\u20102021 and had their samples preserved for DNA extraction were included in this study. An equal number of severity\u2010matched HA patients without inhibitors were also included as controls. Intron 22 and intron 1 inversions in Factor VIII gene were identified using inverse\u2010shifting\u2010PCR. Inversion\u2010negative patients were further assessed by targeted NGS, MLPA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Thirty HA\u2010patients with inhibitors were identified. All had severe\u2010HA. Thirty severe\u2010HA\u2010patients without inhibitors were also included as controls. Intron 22 inversion (63.3%) and large deletions (15%) were the commonest variants identified. There was no difference in genetic variants in patients with low and high titre inhibitors. A3, A2 and C2 were the most common domains involved in inversion\u2010negative patients with inhibitors. However, there was no significant difference in domain involvement among inversion\u2010negative patients with and without inhibitors. Seven novel\u2010variants were identified, including three large deletions, one large duplication and two nonsense variants in inhibitor\u2010positive patients, and one frameshift variant in inhibitor\u2010negative patient. After adjusting for clinical risk\u2010factors, large deletions were independently associated with the presence of inhibitors [aOR:6.1 (1.41\u201056.3)].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Intron 22 inversions are the commonest variant in Indian patients with severe\u2010HA. Large deletions predispose to inhibitor development independent of clinical risk factors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/hae.14948","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T01:05:43Z","timestamp":1707699943000},"page":"410-418","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Unearthing the genotype\u2010inhibitor phenotype association in severe haemophilia A: A north Indian cohort study"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6290-166X","authenticated-orcid":false,"given":"Debadrita","family":"Ray","sequence":"first","affiliation":[{"name":"Department of Hematology Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritika","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Hematology Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narender","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Hematology Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chander","family":"Hans","sequence":"additional","affiliation":[{"name":"Department of Hematology Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harikishan","family":"Senee","sequence":"additional","affiliation":[{"name":"Department of Hematology Postgraduate Institute of Medical Education and Research  Chandigarh 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India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Bansal","sequence":"additional","affiliation":[{"name":"Department of Hematology Paediatrics Postgraduate Institute of Medical Education and Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arihant","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Hematology Clinical Hematology and Medical Oncology Postgraduate Institute of Medical Education and Research  Chandigarh 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