{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:08:50Z","timestamp":1780553330313,"version":"3.54.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"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. Behav. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Wiskott\u2013Aldrich syndrome protein family member 1 (\n                      <jats:italic>WASF1<\/jats:italic>\n                      ) truncating variants, such as c.1516C&amp;gt;T (p.Arg506Ter), are established causes of neurodevelopmental disorders (NDDs), but their underlying pathogenic mechanism remains debated. This study aimed to clarify the disease mechanism and identify potential therapeutic leads.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We characterized a novel, asymptomatic\n                      <jats:italic>WASF1<\/jats:italic>\n                      truncating variant (c.873delA) and compared its clinical and molecular consequences with those of the known pathogenic c.1516C&amp;gt;T variant. To target the likely pathogenic mutant protein, we performed high\u2011throughput virtual screening of the ZINC20 database.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Despite a similar reduction in wild\u2011type protein levels, the c.873delA variant did not cause neurological symptoms, in contrast to c.1516C&amp;gt;T. This observation supports a dominant\u2011negative, gain\u2011of\u2011function, or altered protein function mechanism rather than simple haploinsufficiency; however, the precise mechanism could not be definitively resolved from the available genetic and protein expression data. Virtual screening identified ZINC000101023849 as a high\u2011affinity lead compound with favorable drug\u2011like properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      This study provides key evidence that\n                      <jats:italic>WASF1<\/jats:italic>\n                      \u2011related NDDs likely arise from a non\u2011haploinsufficiency mechanism and delivers a promising chemical lead for targeted therapy development. Further studies are needed to confirm the exact pathogenic mechanism and to validate the therapeutic potential of the identified compound.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnbeh.2026.1822055","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:40:22Z","timestamp":1780551622000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["An asymptomatic WASF1 truncation reveals pathogenic mechanism and therapeutic strategy for neurodevelopmental disorders"],"prefix":"10.3389","volume":"20","author":[{"given":"Shaojuan","family":"Song","sequence":"first","affiliation":[{"name":"Basic Medical College of Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongli","family":"Yang","sequence":"additional","affiliation":[{"name":"Basic Medical College of Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanchun","family":"Gao","sequence":"additional","affiliation":[{"name":"Basic Medical College of Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Clinical College of Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Basic Medical College of Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Basic Medical College of Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuying","family":"Yang","sequence":"additional","affiliation":[{"name":"Basic Medical College of Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Chen","sequence":"additional","affiliation":[{"name":"Basic Medical College of Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Wang","sequence":"additional","affiliation":[{"name":"Basic Medical College of Changzhi Medical College","place":["Changzhi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1242\/jcs.199570","article-title":"Cellular functions of WASP family proteins at a glance","volume":"130","author":"Alekhina","year":"2017","journal-title":"J. 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