{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T01:18:19Z","timestamp":1770599899750,"version":"3.49.0"},"reference-count":13,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T00:00:00Z","timestamp":1716940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nuclear Speckle Splicing Regulator Protein 1 (NSRP1) is a splice factor found in nuclear speckles, which are small membrane\u2010free organelles implicated in epigenetic regulation, chromatin organization, DNA repair, and RNA modification. Bi\u2010allelic loss\u2010of\u2010function variants in NSRP1 have recently been identified in patients suffering from a severe neurodevelopmental disorder, presenting with neurodevelopmental delay, epilepsy, microcephaly, hypotonia, and spastic cerebral palsy. Described patients acquired neither independent walking nor speech and often showed anomalies on cerebral MRI. Here we describe the case of a 14\u2010year\u2010old girl with motor and language delay as well as intellectual disability, who presents an ataxic gait but walks without assistance and speaks in short sentences. Whole\u2010genome sequencing revealed the compound heterozygous NSRP1 variants c.114\u2009+\u20092T\u2009&gt;\u2009G and c.1595T\u2009&gt;\u2009A (p.Val532Glu). Functional validation using HEK293T cells transfected with either wild\u2010type or mutated GFP\u2010tagged <jats:italic>Nsrp1<\/jats:italic> suggests that the Val532Glu variant interferes with the function of the nuclear localization signal, and leads to mislocalization of NSRP1 in the cytosol, thus confirming the pathogenicity of the observed variant. This case helps to expand the phenotypic and genetic spectrum associated with pathogenic NSRP1 variants and indicates that this diagnosis should also be suspected in patients with milder phenotypes.<\/jats:p>","DOI":"10.1002\/ajmg.a.63727","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T12:15:17Z","timestamp":1716984917000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A milder form of NSRP1\u2010associated neurodevelopmental disorder, caused by a missense variant in the nuclear localization signal"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2979-3764","authenticated-orcid":false,"given":"Sebastian","family":"Neuens","sequence":"first","affiliation":[{"name":"Department of Genetics, H\u00f4pital Universitaire Des Enfants Reine Fabiola, H\u00f4pital Universitaire de Bruxelles Universit\u00e9 Libre de Bruxelles  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiza","family":"Kausar","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Immune Synapse and Cell Therapy Research Center Gwangju Institute of Science and Technology (GIST)  Gwangju South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun\u2010Kyoung","family":"Kang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Immune Synapse and Cell Therapy Research Center Gwangju Institute of Science and Technology (GIST)  Gwangju South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Soblet","sequence":"additional","affiliation":[{"name":"Department of Genetics, H\u00f4pital Universitaire Des Enfants Reine Fabiola, H\u00f4pital Universitaire de Bruxelles Universit\u00e9 Libre de Bruxelles  Brussels Belgium"},{"name":"Center for Human Genetics, H\u00f4pital Erasme, H\u00f4pital Universitaire de Bruxelles Universit\u00e9 Libre de Bruxelles  Brussels Belgium"},{"name":"Interuniversity Institute of Bioinformatics in Brussels (IB)<sup>2<\/sup> Universit\u00e9 Libre de Bruxelles\u2010Vrije Universiteit Brussel  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Van Dooren","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Bioinformatics in Brussels (IB)<sup>2<\/sup> Universit\u00e9 Libre de Bruxelles\u2010Vrije Universiteit Brussel  Brussels Belgium"},{"name":"Interuniversity Genomics High Throughput Core (BRIGHTcore), Vrije Universiteit Brussel (VUB) Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"},{"name":"Vrije Universiteit Brussel (VUB), Clinical Sciences, Research Group Genetics, Reproduction and Development (GRAD), Centre for Medical Genetics Universitair Ziekenhuis Brussel (UZ Brussel)  Jette Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catharina","family":"Olsen","sequence":"additional","affiliation":[{"name":"Interuniversity Institute of Bioinformatics in Brussels (IB)<sup>2<\/sup> Universit\u00e9 Libre de Bruxelles\u2010Vrije Universiteit Brussel  Brussels Belgium"},{"name":"Interuniversity Genomics High Throughput Core (BRIGHTcore), Vrije Universiteit Brussel (VUB) Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"},{"name":"Vrije Universiteit Brussel (VUB), Clinical Sciences, Research Group Genetics, Reproduction and Development (GRAD), Centre for Medical Genetics Universitair Ziekenhuis Brussel (UZ Brussel)  Jette Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toon","family":"Janssen","sequence":"additional","affiliation":[{"name":"Interuniversity Genomics High Throughput Core (BRIGHTcore), Vrije Universiteit Brussel (VUB) Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"},{"name":"Vrije Universiteit Brussel (VUB), Clinical Sciences, Research Group Genetics, Reproduction and Development (GRAD), Centre for Medical Genetics Universitair Ziekenhuis Brussel (UZ Brussel)  Jette Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Caljon","sequence":"additional","affiliation":[{"name":"Interuniversity Genomics High Throughput Core (BRIGHTcore), Vrije Universiteit Brussel (VUB) Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"},{"name":"Vrije Universiteit Brussel (VUB), Clinical Sciences, Research Group Genetics, Reproduction and Development (GRAD), Centre for Medical Genetics Universitair Ziekenhuis Brussel (UZ Brussel)  Jette Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang\u2010Duk","family":"Jun","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Immune Synapse and Cell Therapy Research Center Gwangju Institute of Science and Technology (GIST)  Gwangju South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillaume","family":"Smits","sequence":"additional","affiliation":[{"name":"Department of Genetics, H\u00f4pital Universitaire Des Enfants Reine Fabiola, H\u00f4pital Universitaire de Bruxelles Universit\u00e9 Libre de Bruxelles  Brussels Belgium"},{"name":"Center for Human Genetics, H\u00f4pital Erasme, H\u00f4pital Universitaire de Bruxelles Universit\u00e9 Libre de Bruxelles  Brussels Belgium"},{"name":"Interuniversity Institute of Bioinformatics in Brussels (IB)<sup>2<\/sup> Universit\u00e9 Libre de Bruxelles\u2010Vrije Universiteit Brussel  Brussels Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Coppens","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, H\u00f4pital Erasme, H\u00f4pital Universitaire de Bruxelles Universit\u00e9 Libre de Bruxelles  Brussels 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