{"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":1786978268764,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T00:00:00Z","timestamp":1679184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of\u00a0Hunan Province","doi-asserted-by":"publisher","award":["2021JJ70005"],"award-info":[{"award-number":["2021JJ70005"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Neurodevelopmental disorders associated with periventricular nodular heterotopia (PVNH) are characterized by phenotypic and genetic heterogeneity.\n                      <jats:italic>NEDD4L<\/jats:italic>\n                      mutation can lead to PVNH7. However, at present, only eight\n                      <jats:italic>NEDD4L<\/jats:italic>\n                      pathogenic variants have been identified across 15 cases of PVNH7 worldwide. Given this dearth of evidence, the precise correlations between genetic pathogenesis and phenotypes remain to be determined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This report discusses the case of a 19\u2010month\u2010old male child with cleft palate, seizures, psychomotor retardation, and hypotonia, for whom we verified the genetic etiology using Trio\u2010whole\u2010exome and Sanger sequencing to analyze the potential pathogenicity of the mutant protein structure. Mutant plasmids were constructed for in vitro analyses. After transfection into human 293\u2009T cells, the mutant transcription process was analyzed using real\u2010time PCR (RT\u2010PCR), and levels of mutant protein expression were examined using western blotting (WB) and immunofluorescence (IF) experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Genetic analyses revealed a novel missense mutation Gln900Arg, located in the homologous to E6\u2010APC terminal (HECT) domain of\n                      <jats:italic>NEDD4L<\/jats:italic>\n                      and that the parents were wild\u2010type, suggestive of a de novo mutation. The variant was predicted to be pathogenic by bioinformatics software, which also suggested alterations in the structural stability of the mutant protein. RT\u2010PCR results indicated that the mutation did not affect mRNA expression, whereas WB and IF results indicated that the level of mutant protein was significantly reduced by 41.07%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Functional experiments demonstrated that Gln900Arg probably did not lead to transcriptional abnormalities in this patient, instead leading to increased ubiquitination activity owing to the constitutive activation of the HECT domain, thereby promoting protein degradation. Extensive clinical reports should be generated for patients presenting with PVNH and\/or polymicrogyria, developmental delay, syndactyly, and hypotonia to increase the pool of evidence related to\n                      <jats:italic>NEDD4L<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.2169","type":"journal-article","created":{"date-parts":[[2023,3,19]],"date-time":"2023-03-19T13:28:45Z","timestamp":1679232525000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic analysis of periventricular nodular heterotopia 7 caused by a novel\n                    <i>NEDD4L<\/i>\n                    missense mutation: Case and literature summary"],"prefix":"10.1002","volume":"11","author":[{"given":"Juan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Hunan Children's Hospital  Changsha 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