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We identified a novel intronic hemizygous variant (NM_014728.3:c.1198\u20106C&gt;A) in\n                    <jats:italic>FRMPD4<\/jats:italic>\n                    in a 2\u2010year\u2010old male patient with moderate developmental delay inherited from his asymptomatic heterozygous mother. Minigene assays in different cell lines demonstrated that this variant led to the consistent skipping of in\u2010frame exon 12, which encodes 30 amino acids within the FERM domain. We speculated that this splicing defect may be due to the impaired recruitment of essential splicing factor U2AF2, as this C&gt;A intronic variant is positioned at the center of the uridine\u2010rich polypyrimidine tract, adjacent to the 3\u2032\u2010splice site. Structural modeling predicted that the loss of this region would disrupt the integrity of the FERM domain. Given that FRMPD4 mediates metabotropic glutamate receptor signaling via its FERM domain, we conclude that this intronic variant is likely pathogenic.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64306","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T11:20:22Z","timestamp":1763119222000},"page":"892-898","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Intronic Variant in\n                    <scp>\n                      <i>FRMPD4<\/i>\n                    <\/scp>\n                    Disrupts Splicing: Case Report of an X\u2010Linked Neurodevelopmental Disorder"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3380-8121","authenticated-orcid":false,"given":"Tomoko","family":"Satake","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"},{"name":"Clinical Research Institute Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Kawai","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koki","family":"Nagai","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Naruto","sequence":"additional","affiliation":[{"name":"Clinical Research Institute Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center  Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"issue":"6","key":"e_1_2_11_2_1","first-page":"1229","article-title":"Methylation of HpaII and HhaI Sites Near the Polymorphic CAG Repeat in the Human Androgen\u2010Receptor Gene Correlates With X Chromosome Inactivation","volume":"51","author":"Allen R. 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