{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:03:33Z","timestamp":1793905413081,"version":"4.8.0"},"reference-count":16,"publisher":"BMJ","issue":"7","funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2018,3,2]]},"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>Overhydrated stomatocytosis is a rare autosomal dominant disorder known to cause variably severe haemolytic anaemia due to heterozygous mutations in the <jats:italic>RHAG<\/jats:italic> gene. We report a 26-year-old man with recurring jaundice, splenohepatomegaly and mild chronic haemolytic anaemia with significant stomatocytosis. Extensive haemolytic work-up including flow cytometry for eosin-5\u2032-maleimide and CD47 expression levels was carried out. Targeted resequencing revealed two probably causative heterozygous mutations in <jats:italic>RHAG<\/jats:italic> (Leu336Ser and Ile149Met) and one heterozygous mutation in <jats:italic>ANK1<\/jats:italic> (Glu1046Lys)<jats:italic>. RHAG<\/jats:italic> involvement was confirmed by decreased RhAG macrocomplex component indicated by the reduced CD47 expression on erythrocytes. <jats:italic>In silico<\/jats:italic> analysis concordantly flagged <jats:italic>RHAG<\/jats:italic>:Leu336Ser and <jats:italic>ANK1<\/jats:italic>:Glu1046Lys as likely deleterious mutation, whereas <jats:italic>RHAG<\/jats:italic>:Ile149Met was reported as likely neutral by PROVEAN. Family screening by Sanger sequencing revealed <jats:italic>RHAG<\/jats:italic>:Leu336Ser in a mother and <jats:italic>ANK1<\/jats:italic>:Glu1046Lys in a father who were both asymptomatic, excluding them as causative dominant events, thus establishing <jats:italic>RHAG<\/jats:italic>:Ile149Met, novel <jats:italic>de novo<\/jats:italic> mutation as probably causative. This case illustrates the importance of family screening in interpreting next-generation sequencing (NGS) data, as in silico analysis alone can be misleading. Erudite generation of diagnostic possibilities based on a thorough baseline clinical and laboratory work-up remains as important as ever, even as NGS brings about a paradigm shift in the diagnostic work-up of rare haemolytic anaemias.<\/jats:p>","DOI":"10.1136\/jclinpath-2018-205018","type":"journal-article","created":{"date-parts":[[2018,3,20]],"date-time":"2018-03-20T12:15:24Z","timestamp":1521548124000},"page":"648-652","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Overhydrated stomatocytosis associated with a complex <i>RHAG<\/i> genotype including a novel <i>de novo<\/i> mutation"],"prefix":"10.1136","volume":"71","author":[{"given":"Manu","family":"Jamwal","sequence":"first","affiliation":[{"name":"Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anu","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man Updesh Singh","family":"Sachdeva","sequence":"additional","affiliation":[{"name":"Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4741-3403","authenticated-orcid":false,"given":"Prashant","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arindam","family":"Maitra","sequence":"additional","affiliation":[{"name":"National Institute of Biomedical Genomics, Kalyani, West Bengal, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8938-5423","authenticated-orcid":false,"given":"Reena","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2018,3,20]]},"reference":[{"key":"2025092612091774000_71.7.648.1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/ijlh.12357","article-title":"Disorders of erythrocyte volume homeostasis","volume":"37 Suppl 1","author":"Glogowska","year":"2015","journal-title":"Int J Lab Hematol"},{"key":"2025092612091774000_71.7.648.2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1179\/1607845413Y.0000000149","article-title":"Values of mean cell volume and mean sphered cell volume can differentiate hereditary spherocytosis and thalassemia","volume":"19","author":"Liao","year":"2014","journal-title":"Hematology"},{"key":"2025092612091774000_71.7.648.3","doi-asserted-by":"crossref","unstructured":"Ciepiela O , Adamowicz-Salach A , Zgodzi\u0144ska A , et al . 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