{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:08:30Z","timestamp":1785434910182,"version":"3.56.0"},"reference-count":31,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-75-30015"],"award-info":[{"award-number":["21-75-30015"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["21-75-30015"],"award-info":[{"award-number":["21-75-30015"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by biallelic loss of function variants in the SLC19A2 gene. It typically presents with a triad of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. In this work, we analyzed ten children with suspected TRMA: nine exhibited the full triad and one, a younger sibling of a patient with full triad, did not develop hearing loss by the age of 18 months. All patients became transfusion-independent on high-dose thiamine therapy. Whole-genome sequencing identified homozygosity for the canonical splice variant SLC19A2 c.1223+1G&gt;A in eight patients. One patient was homozygous for a known SLC19A2 c.196G&gt;T variant, and the other was compound heterozygous for two novel variants, c.120C&gt;G and c.584T&gt;C. All patients with the SLC19A2 c.1223+1G&gt;A variant were ethnic Ingush. In the reference Ingush cohort, 9\/328 unrelated adults were c.1223+1G&gt;A carriers (heterozygous carrier frequency 2.7%; carrier frequency \u2248 1\/36), and shared a 2.3 Mb ATP1B1\u2013FMO2 haplotype on chromosome 1, demonstrating a strong founder effect. These findings identify Ingushetia as a new TRMA-endemic region and support targeted SLC19A2 screening and early thiamine therapy in patients with macrocytic anemia and diabetes of unclear origin in this population.<\/jats:p>","DOI":"10.3390\/ijms27146274","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T03:06:52Z","timestamp":1784084812000},"page":"6274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Endemic Region of Thiamine-Responsive Megaloblastic Anemia Caused by an SLC19A2 c.1223+1G&gt;A Founder Mutation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0411-9485","authenticated-orcid":false,"given":"Medina","family":"Gurzhikhanova","sequence":"first","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, 117198 Moscow, Russia"},{"name":"Biotech Campus LLC, 117437 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei","family":"Fomenko","sequence":"additional","affiliation":[{"name":"Biotech Campus LLC, 117437 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1131-3195","authenticated-orcid":false,"given":"Nikolay","family":"Chekanov","sequence":"additional","affiliation":[{"name":"Biotech Campus LLC, 117437 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Musharova","sequence":"additional","affiliation":[{"name":"Biotech Campus LLC, 117437 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Salimova","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Goronkova","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9179-8430","authenticated-orcid":false,"given":"Ruslan","family":"Abasov","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Raykina","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3586-3458","authenticated-orcid":false,"given":"Rena","family":"Zinchenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3148-6915","authenticated-orcid":false,"given":"Margarita","family":"Sharova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fizaliia","family":"Khisamieva","sequence":"additional","affiliation":[{"name":"The State Autonomous Healthcare Institution \u201cChildren\u2019s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan\u201d, 420064 Kazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4529-7891","authenticated-orcid":false,"given":"Evgeny","family":"Imyanitov","sequence":"additional","affiliation":[{"name":"Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, 197758 Saint Petersburg, Russia"},{"name":"Department of Medical Genetics, St.-Petersburg Pediatric Medical University, 194100 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6304-1609","authenticated-orcid":false,"given":"Anna","family":"Sokolenko","sequence":"additional","affiliation":[{"name":"Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, 197758 Saint Petersburg, Russia"},{"name":"Department of Medical Genetics, St.-Petersburg Pediatric Medical University, 194100 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5314-038X","authenticated-orcid":false,"given":"Evgeny","family":"Klimuk","sequence":"additional","affiliation":[{"name":"Biotech Campus LLC, 117437 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Maschan","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9706-450X","authenticated-orcid":false,"given":"Konstantin","family":"Severinov","sequence":"additional","affiliation":[{"name":"Biotech Campus LLC, 117437 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1735-0093","authenticated-orcid":false,"given":"Michael","family":"Maschan","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/S0022-3476(69)80031-4","article-title":"Thiamine-Responsive Megaloblastic Anemia","volume":"74","author":"Rogers","year":"1969","journal-title":"J. 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