{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T21:45:02Z","timestamp":1791755102186,"version":"4.3.4"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec>\n            <jats:title>Introduction<\/jats:title>\n            <jats:p>Biallelic variants in thiamine pyrophosphokinase 1 (<jats:italic toggle=\"yes\">TPK1<\/jats:italic>) are known to cause thiamine metabolism dysfunction syndrome 5 (THMD5). This disorder is characterized by neuroregression, ataxia and dystonia with basal ganglia abnormalities on neuroimaging. To date, 27 families have been reported with THMD5 due to variants in <jats:italic toggle=\"yes\">TPK1<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We ascertained three individuals from three unrelated families. Singleton exome sequencing was performed on all three individuals, followed by <jats:italic toggle=\"yes\">in silico<\/jats:italic> mutagenesis of the mutant TPK protein. Additionally, we reviewed the genotypic and phenotypic information of 27 previously reported individuals with THMD5.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Singleton exome sequencing revealed a novel homozygous variant c.620A&gt;T p.(Asp207Val) in <jats:italic toggle=\"yes\">TPK1<\/jats:italic> (NM_022445.4) in all three individuals. <jats:italic toggle=\"yes\">In silico<\/jats:italic> mutagenesis of the mutant protein revealed a decrease in protein stability and altered interactions with its neighboring residues compared to the wild-type protein. Thus, based on strikingly similar clinical and radiological findings compared to the previously reported individuals and with the support of <jats:italic toggle=\"yes\">in silico<\/jats:italic> mutagenesis findings, the above-mentioned variant appears to be the probable cause for the condition observed in the affected individuals in this study.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>We report a novel homozygous variant in <jats:italic toggle=\"yes\">TPK1<\/jats:italic>, which appears to be recurrent among the Indian population.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/mcd.0000000000000490","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T12:00:15Z","timestamp":1723636815000},"page":"160-166","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Report of a novel recurrent homozygous variant c.620A&gt;T in three unrelated families with thiamine metabolism dysfunction syndrome 5 and review of literature"],"prefix":"10.1097","volume":"33","author":[{"given":"Selinda","family":"Mascarenhas","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayuri","family":"Yeole","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi Priya","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle C","family":"do Rosario","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purvi","family":"Majethia","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik Vijay","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvasini","family":"Sharma","sequence":"additional","affiliation":[{"name":"Neurology Division, Department of Pediatrics, Lady Hardinge Medical College and Associated Kalawati Saran Children\u2019s Hospital, New 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