{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:09:54Z","timestamp":1791317394334,"version":"4.3.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T00:00:00Z","timestamp":1646870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003785","name":"Guangdong Medical Research Foundation","doi-asserted-by":"publisher","award":["A2020257"],"award-info":[{"award-number":["A2020257"]}],"id":[{"id":"10.13039\/501100003785","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1414020008"],"award-info":[{"award-number":["2021A1414020008"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Recessive mutations in <jats:italic>BRAT1<\/jats:italic> cause lethal neonatal rigidity and multifocal seizure syndrome (RMFSL), a phenotype characterized by neonatal microcephaly, hypertonia, and refractory epilepsy with premature death. Recently, attenuated disease variants have been described, suggesting that a wider clinical spectrum of <jats:italic>BRAT1<\/jats:italic>-associated neurodegeneration exists than was previously thought. Here, we reported a 10-year-old girl with severe intellectual disability, rigidity, ataxia or dyspraxia, and cerebellar atrophy on brain MRI; two <jats:italic>BRAT1<\/jats:italic> variants in the <jats:italic>trans<\/jats:italic> configuration [c.1014A &amp;gt; C (p.Pro338 = ); c.706delC (p.Leu236Cysfs*5)] were detected using whole-exome sequencing. RNA-seq confirmed significantly decreased <jats:italic>BRAT1<\/jats:italic> transcript levels in the presence of the variant; further, it revealed an intron retention between exon 7 and exon 8 caused by the synonymous base substitute. Subsequent prenatal diagnosis for these two variants guided the parents to reproduce. We expand the phenotypic spectrum of <jats:italic>BRAT1<\/jats:italic>-associated disorders by first reporting the pathogenic synonymous variant of the <jats:italic>BRAT1<\/jats:italic> gene, resulting in clinical severity that is mild compared to the severe phenotype seen in RMFSL. Making an accurate diagnosis and prognostic evaluation of <jats:italic>BRAT1<\/jats:italic>-associated neurodegeneration is important for reproductive consultation and disease management.<\/jats:p>","DOI":"10.3389\/fgene.2022.821587","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T12:05:10Z","timestamp":1646913910000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Novel Biallelic Variant in the BRAT1 Gene Caused Nonprogressive Cerebellar Ataxia Syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Yiming","family":"Qi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqi","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongke","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihua","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1101\/gad.247361.114","article-title":"Detained Introns Are a Novel, Widespread Class of post-transcriptionally Spliced Introns","volume":"29","author":"Boutz","year":"2015","journal-title":"Genes Dev."},{"key":"B2","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.ebcr.2017.05.003","article-title":"Lethal Neonatal Rigidity and Multifocal Seizure Syndrome with a New Mutation in BRAT1","volume":"8","author":"Celik","year":"2017","journal-title":"Epilepsy Behav. 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