{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T12:46:17Z","timestamp":1782305177067,"version":"3.54.5"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100014895","name":"Southwest Medical University","doi-asserted-by":"publisher","award":["00040164"],"award-info":[{"award-number":["00040164"]}],"id":[{"id":"10.13039\/501100014895","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014895","name":"Southwest Medical University","doi-asserted-by":"publisher","award":["2025SKLYB04"],"award-info":[{"award-number":["2025SKLYB04"]}],"id":[{"id":"10.13039\/501100014895","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen & Gen Med"],"published-print":{"date-parts":[[2026,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by mutations in\n TYMP<\/jats:italic>\n , which disrupt thymidine metabolism. This study aimed to characterize a novel homozygous\n TYMP<\/jats:italic>\n variant and provide insights into its potential structural and functional consequences through bioinformatic analyses.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We identified a homozygous\n TYMP<\/jats:italic>\n variant (c.131G>C, p.R44P) in a proband with MNGIE using whole\u2010exome sequencing and Sanger sequencing. Computational structural analyses and molecular modeling were performed to predict the impact of the R44P substitution on thymidine phosphorylase (TP) stability, homodimerization, catalytic activity, and substrate binding.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The homozygous\n TYMP<\/jats:italic>\n c.131G>C variant was confirmed in the proband. Computational analyses suggested that the p.R44P substitution may destabilize TP and potentially impair homodimerization. Molecular modeling further predicted altered thymidine binding and disrupted active\u2010site geometry. These predicted perturbations are hypothesized to contribute to defective nucleotide metabolism, thymidine accumulation, and deoxynucleotide triphosphate pool imbalance, which may ultimately result in mitochondrial genomic instability manifesting as mitochondrial DNA deletions and depletion.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our findings report the\n TYMP<\/jats:italic>\n c.131G>C variant in a homozygous configuration, extending beyond a recently described compound heterozygous case. The bioinformatic predictions support the classification of this variant as likely pathogenic in MNGIE, though functional studies are warranted to validate these findings.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.70253","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:18:16Z","timestamp":1781756296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of a Homozygous\n TYMP<\/i>\n c.\n 131G<\/scp>\n >C Variant With\n MNGIE<\/scp>\n in a Chinese Pedigree: Insights From Genetic Analysis and Computational Modeling"],"prefix":"10.1002","volume":"14","author":[{"given":"Ling","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Hospital of Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Affiliated Hospital of Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5037-4583","authenticated-orcid":false,"given":"Kai","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology and Genetics, School of Basic Medical Sciences Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1472-0999","authenticated-orcid":false,"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology and Genetics, School of Basic Medical Sciences Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6207-1547","authenticated-orcid":false,"given":"Mingyi","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology and Genetics, School of Basic Medical Sciences Southwest Medical University Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0414-9895","authenticated-orcid":false,"given":"Songhua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medical Cell Biology and Genetics, School of Basic Medical Sciences Southwest Medical University Luzhou 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