{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:08:54Z","timestamp":1790384934383,"version":"4.1.0"},"reference-count":26,"publisher":"BMJ","issue":"10","funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology","doi-asserted-by":"publisher","award":["Grant no. BT\/PR20782\/MED\/12\/737\/16"],"award-info":[{"award-number":["Grant no. BT\/PR20782\/MED\/12\/737\/16"]}],"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":[[2020,12,1]]},"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p>\n                    Hexokinase (EC 2.7.1.1, Adenosine Tri Phosphate (ATP): D-hexose-6-phosphotransferase) is a crucial regulatory enzyme of the glycolytic pathway (Embden-Meyerhof pathway). Hexokinase deficiency is associated with chronic non-spherocytic haemolytic anaemia (HA) with some exceptional cases showing psychomotor\/mental retardation and fetus death. The proband is a four-and-half-year-old female child born of a four-degree consanguineous marriage hailing from South India with autosomal recessive congenital HA associated with developmental delay. She was well till 3 months of her age post an episode of diarrhoea when she was noted to be severely anaemic and requiring regular transfusions. The common causes of HA, haemoglobinopathies, red cell membranopathies and common red cell enzymopathies (G6PD, GPI, PK and P5N) were ruled out. Targeted analysis of whole exome sequencing (WES) using an insilico gene panel for hereditary anaemia was performed to identify pathogenic variants in the patient. Next-generation sequencing revealed a novel homozygous variant in hexokinase gene c.2714C&gt;A (p. Thr905Lys) in exon-18. The pathogenic nature of the variant p. Thr905Lys in the\n                    <jats:italic>HK1<\/jats:italic>\n                    gene was confirmed collectively by biochemical and molecular studies. Insilico analysis (PolyPhen-2, Provean, Mutation Taster) predicted the variant to be severe disease causing. Multiple sequence alignment demonstrated the conservation of p. Thr905 across the species. The impact of the mutation on the protein structure was studied by PyMOL and Swiss Protein databank viewer.\n                  <\/jats:p>","DOI":"10.1136\/jclinpath-2020-206960","type":"journal-article","created":{"date-parts":[[2020,12,25]],"date-time":"2020-12-25T13:25:13Z","timestamp":1608902713000},"page":"620-624","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Novel pathogenic variant c.2714C&gt;A (p. Thr905Lys) in the\n                    <i>HK1<\/i>\n                    gene causing severe haemolytic anaemia with developmental delay in an Indian family"],"prefix":"10.1136","volume":"74","author":[{"given":"Rashmi","family":"Dongerdiye","sequence":"first","affiliation":[{"name":"Hematogenetics, National Institute of Immunohaematology, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujatha","family":"Jagadeesh","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genetic Counseling Department, MediScan Systems, Chennai, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beena","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genetic Counseling Department, MediScan Systems, Chennai, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruna","family":"Rajendran","sequence":"additional","affiliation":[{"name":"Department of Hematology, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rati","family":"Devendra","sequence":"additional","affiliation":[{"name":"Hematogenetics, National Institute of Immunohaematology, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant","family":"Warang","sequence":"additional","affiliation":[{"name":"Hematogenetics, National Institute of Immunohaematology, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3509-2913","authenticated-orcid":false,"given":"Prabhakar S","family":"Kedar","sequence":"additional","affiliation":[{"name":"Hematogenetics, National Institute of Immunohaematology, Mumbai, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,12,25]]},"reference":[{"key":"2025121219302811000_74.10.620.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2016.04.002"},{"key":"2025121219302811000_74.10.620.2","first-page":"4034","volume":"106","author":"Van Wijk","year":"2005","journal-title":"van Solingen WW.: The energy-less red blood cell is lost erythrocyte enzyme abnormalities of glycolysis. 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