{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:51:08Z","timestamp":1786978268707,"version":"build-2736575974"},"reference-count":17,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen & Gen Med"],"published-print":{"date-parts":[[2022,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n A de novo, pathogenic, missense variant in\n UBTF<\/jats:italic>\n , c.628G>A p.Glu210Lys, has been described as the cause of an emerging neurodegenerative disorder, Childhood\u2010Onset Neurodegeneration with Brain Atrophy (CONDBA). The p.Glu210Lys alteration yields a positively charged stretch of three lysine residues. Functional studies confirmed this change results in a stronger interaction with negatively charged DNA and gain\u2010of\u2010function activity when compared to the wild\u2010type sequence. The CONDBA phenotype reported in association with p.Glu210Lys consists of normal early\u2010neurodevelopment followed by progressive motor, cognitive, and behavioral regression in early\u2010to\u2010middle childhood.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n The current proband presented at 9 months of age with baseline developmental delay and more extensive neuroradiological findings, including pontine hypoplasia, thalamic volume loss and signal abnormality, and hypomyelination. Like the recurrent CONDBA p.Glu210Lys variant, this novel variant, c.608A>G p.(Gln203Arg) lies within the highly conserved second HMG\u2010box homology domain and involves the replacement of the wild\u2010type residue with a positively charged residue, arginine. Computational structural modeling demonstrates that this amino acid substitution potentiates the interaction between\n UBTF<\/jats:italic>\n and DNA, likely resulting in a gain\u2010of\u2010function effect for the\n UBTF<\/jats:italic>\n protein, UBF.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Here we present a new divergent phenotype associated with a novel, likely pathogenic, missense variant at a different position in the\n UBTF<\/jats:italic>\n gene, c.608A>G p.(Gln203Arg).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mgg3.2054","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T04:41:21Z","timestamp":1663216881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A novel, likely pathogenic variant in\n UBTF<\/i>\n \u2010related neurodegeneration with brain atrophy is associated with a severe divergent neurodevelopmental phenotype"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7093-8844","authenticated-orcid":false,"given":"Rory J.","family":"Tinker","sequence":"first","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Guess","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Rinker","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Vanderbilt University Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Sheehan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Infectious Diseases Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Lubarsky","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binu","family":"Porath","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Mosera","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Mayo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Solem","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asha","family":"Sarma","sequence":"additional","affiliation":[{"name":"Department of Radiology Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Brault","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Genomic 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