{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:29:42Z","timestamp":1777555782758,"version":"3.51.4"},"reference-count":29,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Pathogenic gene variants encoding nuclear pore complex (NPC) proteins were previously implicated in the pathogenesis of steroid-resistant nephrotic syndrome (SRNS). The NUP85 gene, encoding nucleoporin, is related to a very rare form of SRNS with limited genotype\u2013phenotype information. We identified an Italian boy affected with an SRNS associated with severe neurodevelopmental impairment characterized by microcephaly, axial hypotonia, lack of achievement of motor milestones, and refractory seizures with an associated hypsarrhythmic pattern on electroencephalography. Brain magnetic resonance imaging (MRI) showed hypoplasia of the corpus callosum and a simplified gyration of the cerebral cortex. Since the age of 3 years, the boy was followed up at our Pediatric Nephrology Department for an SRNS, with a focal segmental glomerulosclerosis at renal biopsy. The boy died 32 months after SRNS onset, and a Whole-Exome Sequencing analysis revealed a novel compound heterozygous variant in NUP85 (NM_024844.5): 611T&gt;A (p.Val204Glu), c.1904T&gt;G (p.Leu635Arg), inherited from the father and mother, respectively. We delineated the clinical phenotypes of NUP85-related disorders, reviewed the affected individuals so far reported in the literature, and overall expanded both the phenotypic and the molecular spectrum associated with this ultra-rare genetic condition. Our study suggests a potential occurrence of severe neurological phenotypes as part of the NUP85-related clinical spectrum and highlights an important involvement of nucleoporin in brain developmental processes and neurological function.<\/jats:p>","DOI":"10.3390\/genes14122143","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T07:56:10Z","timestamp":1701071770000},"page":"2143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["NUP85 as a Neurodevelopmental Gene: From Podocyte to Neuron"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7421-0903","authenticated-orcid":false,"given":"Antonella","family":"Gambadauro","sequence":"first","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6541-3170","authenticated-orcid":false,"given":"Giuseppe Donato","family":"Mangano","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karol","family":"Galletta","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Dental Science and Morphological and Functional Images, Neuroradiology Unit, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Granata","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Dental Science and Morphological and Functional Images, Neuroradiology Unit, University of Messina, Via Consolare Valeria 1, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Riva","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics, IRCSS Giannina Gaslini Institute, Via Gerolamo Gaslini 5, 16147 Genoa, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Via Gerolamo Gaslini 5, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Massella","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatric Subspecialties, Bambino Ges\u00f9 Children\u2019s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabella","family":"Guzzo","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatric Subspecialties, Bambino Ges\u00f9 Children\u2019s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Farello","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Scorrano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3889-1318","authenticated-orcid":false,"given":"Ludovica","family":"Di Francesco","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3979-9265","authenticated-orcid":false,"given":"Giulio","family":"Di Donato","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Ianni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-1475","authenticated-orcid":false,"given":"Armando","family":"Di Ludovico","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1244-0789","authenticated-orcid":false,"given":"Saverio","family":"La Bella","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-1476","authenticated-orcid":false,"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics, IRCSS Giannina Gaslini Institute, Via Gerolamo Gaslini 5, 16147 Genoa, Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Via Gerolamo Gaslini 5, 16147 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4900-9877","authenticated-orcid":false,"given":"Stephanie","family":"Efthymiou","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[{"name":"Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosaria","family":"Nardello","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9143-4637","authenticated-orcid":false,"given":"Roberto","family":"Chimenz","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \u201cGaetano Barresi\u201d, University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1080\/20469047.2017.1374003","article-title":"Nephrotic syndrome in infants and children: Pathophysiology and management","volume":"37","author":"Downie","year":"2017","journal-title":"Paediatr. 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