{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:39:31Z","timestamp":1793230771403,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004156","name":"Mahidol University","doi-asserted-by":"publisher","award":["CF_63003"],"award-info":[{"award-number":["CF_63003"]}],"id":[{"id":"10.13039\/501100004156","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":[[2022,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Next\u2010generation sequencing has shed light on the diagnosis of previously unsolved cases of inherited haemolytic anaemia (IHA). We employed whole\u2010exome sequencing to explore the molecular diagnostic spectrum of 21 unrelated Thai paediatric patients with non\u2010thalassemic IHA, presenting hydrops fetalis and\/or becoming transfusion\u2010dependent for 1\u00a0year or more or throughout their lifespan. Anaemia was detected prenatally, within the first month and the fifth year of life in three, 12 and six patients respectively. Molecular diagnosis obtained from all patients revealed <jats:italic>SPTB<\/jats:italic> as the most frequently mutated gene (four reported, three novel), found in 31 of 42 studied alleles. The other two mutated genes identified were <jats:italic>ANK1<\/jats:italic> (three novel) and <jats:italic>KLF1<\/jats:italic> (two reported). Four recurring mutations within exon 29\/30 (NM_001024858.2) accounted for the vast majority (90%) of mutated <jats:italic>SPTB<\/jats:italic> alleles, biallelic inheritance of which resulted in the most severe phenotypes: hydrops fetalis and life\u2010long transfusion dependency. Dominant <jats:italic>ANK1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u20093) and <jats:italic>SPTB<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u20092) mutations and biallelic class 2 <jats:italic>KLF1<\/jats:italic> mutations (<jats:italic>n<\/jats:italic>\u00a0=\u20091) led to a shorter period of transfusion dependency. Our study demonstrated that mutated <jats:italic>SPTB<\/jats:italic> causing red\u2010cell membranopathy is likely the most common cause of severe non\u2010thalassemic IHA among Thai patients. This urges carrier screening in the population to prevent subsequent, severely affected births.<\/jats:p>","DOI":"10.1111\/bjh.18356","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T16:19:40Z","timestamp":1657642780000},"page":"1051-1064","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Whole\u2010exome sequencing uncovered genetic diagnosis of severe inherited haemolytic anaemia: Correlation with clinical phenotypes"],"prefix":"10.1111","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-7211","authenticated-orcid":false,"given":"Duantida","family":"Songdej","sequence":"first","affiliation":[{"name":"Pediatric Hematology\u2010Oncology, Department of Pediatrics Faculty of Medicine Ramathibodi Hospital, Mahidol University  Bangkok 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