{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T10:17:10Z","timestamp":1787825830926,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T00:00:00Z","timestamp":1570665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100012359","name":"Douglas Bomford Trust","doi-asserted-by":"publisher","award":["DBT\/PR14802\/MED\/12\/494\/2010"],"award-info":[{"award-number":["DBT\/PR14802\/MED\/12\/494\/2010"]}],"id":[{"id":"10.13039\/100012359","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":[[2020,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Defects in various erythrocyte membrane proteins genes (ankyrin, band\u20103, \u03b2\u2010 and \u03b1\u2010spectrin and protein 4\u00b72) can cause hereditary spherocytosis (HS). This molecular heterogeneity of HS, together with co\u2010inherited genetic modifiers, results in marked phenotypic variability among patients. We studied the molecular spectrum and genotype\u2010phenotype correlations in 73 families (with 113 patients) with HS. Deleterious variants including nonsense (42%), deletions (18%), splice site (20%), missense (10%) and duplication\/insertion (10%) were found in 47 patients. The variants detected included sporadic and dominantly\u2010inherited defects in <jats:italic>ANK1<\/jats:italic> (53\u00b72%), <jats:italic>SPTB<\/jats:italic> (36\u00b72%) and <jats:italic>SLC4A1<\/jats:italic> (4\u00b72%)<jats:italic>.<\/jats:italic> Compound heterozygous variants in <jats:italic>SPTA1<\/jats:italic> (6\u00b74%) showed autosomal recessive inheritance. Alpha\u2010spectrin variants were associated with severe anaemia and splenectomy alleviated symptoms. Co\u2010inherited glucose\u20106\u2010phosphate dehydrogenase (G6PD) deficiency was found in 15%. G6PD variants (<jats:italic>n<\/jats:italic>\u00a0=\u00a05) led to greater transfusion requirements (1\u20108 times) in males with HS. Homozygosity (41%) for the promoter variant of <jats:italic>UGT1A1<\/jats:italic> (Gilbert syndrome) led to a significantly higher mean bilirubin level (126\u00b754\u00a0\u00b5mol\/l) with a higher frequency of cholelithiasis (30%) (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b7001). This first\u2010ever south Asian study on the molecular spectrum of HS found <jats:italic>ANK1<\/jats:italic> and <jats:italic>SPTB<\/jats:italic> genes variants to be the commonest with inheritance being sporadic\/dominant. Next\u2010generation sequencing provided a relatively sensitive and rapid tool for molecular diagnosis with a diagnostic yield of 64\u00b74%.<\/jats:p>","DOI":"10.1111\/bjh.16244","type":"journal-article","created":{"date-parts":[[2019,10,11]],"date-time":"2019-10-11T05:59:40Z","timestamp":1570773580000},"page":"784-795","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Deciphering molecular heterogeneity of Indian families with hereditary spherocytosis using targeted next\u2010generation sequencing: First South Asian study"],"prefix":"10.1111","volume":"188","author":[{"given":"Anu","family":"Aggarwal","sequence":"first","affiliation":[{"name":"Department of Haematology Postgraduate Institute of Medical Education and Research Chandigarh 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