{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:09:50Z","timestamp":1791317390236,"version":"4.3.1"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Biallelic BRCA1-associated ataxia telangiectasia mutated activator 1 (\n                      <jats:italic>BRAT1<\/jats:italic>\n                      ) gene mutations can result in lethal neonatal rigidity and multifocal seizure syndrome (RMFSL), characterized by refractory epilepsy, hypertonia, autonomic dysfunction, and early death. This study reports an infant with RMFSL bearing novel compound heterozygous\n                      <jats:italic>BRAT1<\/jats:italic>\n                      gene mutations, including a rare pathogenic synonymous variant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A male infant born at 37 weeks of gestation presented with seizures shortly after birth. Clinical features included refractory epilepsy, bilateral clubfoot deformity, and respiratory failure. Whole-exome sequencing identified compound heterozygous\n                      <jats:italic>BRAT1<\/jats:italic>\n                      gene mutations (c.1395G&amp;gt;C, p.Thr465Thr and c.1297delC, p.Leu433Trpfs*). The c.1395G&amp;gt;C variant is a synonymous mutation with a predicted high-risk impact on mRNA splicing, whereas c.1297delC is a previously unreported novel frameshift mutation. These variants were inherited from phenotypically normal, healthy parents.\n                    <\/jats:p>\n                    <jats:p>Despite the provided care, the infant died at one month of age.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This case highlights that synonymous\n                      <jats:italic>BRAT1<\/jats:italic>\n                      variants affecting mRNA splicing can be pathogenic, leading to severe RMFSL. The findings expand the genotypic spectrum and underscore the need for comprehensive bioinformatics analysis of non-coding consequences in genetic testing.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1694328","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T05:22:50Z","timestamp":1770614570000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["BRAT1 gene compound heterozygous mutations causing lethal neonatal rigidity and multifocal seizure syndrome: a case report"],"prefix":"10.3389","volume":"14","author":[{"given":"Dong-Yuan","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Neonatology, The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin-Qin","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Jun","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Huan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Cong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Second Hospital & Clinical Medical School, Lanzhou University","place":["Lanzhou, 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