{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:00:51Z","timestamp":1791475251498,"version":"4.3.4"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"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. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aims to investigate the clinical phenotype and genetic etiology of a case of Ververi\u2013Brady syndrome (VBS) with infantile epileptic spasms syndrome (IESS) caused by a novel\n                      <jats:italic>de novo<\/jats:italic>\n                      variant in the\n                      <jats:italic>QRICH1<\/jats:italic>\n                      gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical data were retrospectively collected from a pediatric patient admitted to Hunan Children\u2019s Hospital on July 28, 2025, due to intermittent nodding episodes for 10\u202fdays. Trio-based whole-exome sequencing (trio-WES) was performed for the proband and his parents. Candidate variants were validated by Sanger sequencing and assessed for pathogenicity. Relevant literature was reviewed to summarize genotype\u2013phenotype correlations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The patient, a 5-month-and-22-day-old male infant, presented with facial dysmorphism, global developmental delay, and IESS. After treatment with adrenocorticotropic hormone (ACTH) and vigabatrin, seizures were fully controlled and developmental outcomes improved. Trio-WES identified a novel heterozygous frameshift variant in the\n                      <jats:italic>QRICH1<\/jats:italic>\n                      gene (NM_198880.3: c.1282dup, p. Gln428Profs*27), which was\n                      <jats:italic>de novo<\/jats:italic>\n                      and absent in both parents. According to the ACMG\/AMP guidelines, this variant was classified as pathogenic (PVS1\u202f+\u202fPS2\u202f+\u202fPM2_Supporting). A literature review identified 11 relevant articles, encompassing a total of 46 patients (including the present case) with 41 distinct\n                      <jats:italic>QRICH1<\/jats:italic>\n                      variants: 10 missense, 11 nonsense, 17 frameshift, and 3 splicing mutations. Common clinical features included developmental delay, nonspecific facial dysmorphism, hypotonia, autism spectrum disorder, epilepsy, and scoliosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>QRICH1<\/jats:italic>\n                      variants underlie Ververi\u2013Brady syndrome. Here we describe a patient with\n                      <jats:italic>QRICH1<\/jats:italic>\n                      -related Ververi\u2013Brady syndrome presenting with IESS. Combined treatment with ACTH and vigabatrin was followed by seizure freedom, electroencephalographic (EEG) improvement, and developmental gains in this patient. This report expands the genotypic and phenotypic spectrum of the disorder.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1848591","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T05:33:57Z","timestamp":1781501637000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel de novo QRICH1 variant causing Ververi\u2013Brady syndrome with infantile epileptic spasms syndrome: clinical and genetic analysis"],"prefix":"10.3389","volume":"20","author":[{"given":"Hongjun","family":"Fang","sequence":"first","affiliation":[{"name":"Department of Neurology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital)","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital)","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital)","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital)","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital)","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital)","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sai","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital)","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital)","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeshu","family":"Ning","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital)","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1001\/jamaneurol.2023.2363","article-title":"Exome sequencing and new genes in polymicrogyria","volume":"80","author":"Akula","year":"2023","journal-title":"JAMA Neurol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.1002\/ajmg.a.62184","article-title":"A case of Ververi\u2013Brady syndrome due to QRICH1 loss of function","volume":"185","author":"Baruch","year":"2021","journal-title":"Am. 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