{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T12:24:49Z","timestamp":1766492689137,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T00:00:00Z","timestamp":1693872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"National Plan on I+D+I, co-financed by ISCIII (Subdirecci\u00f3n General de Evaluaci\u00f3n y Fomento de la Investigaci\u00f3n Sanitaria) and FEDER (Fondo Europeo de Desarrollo Regional)","doi-asserted-by":"publisher","award":["PI18\/00101","FI22\/00218"],"award-info":[{"award-number":["PI18\/00101","FI22\/00218"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Plan on I+D+I","award":["PI18\/00101","FI22\/00218"],"award-info":[{"award-number":["PI18\/00101","FI22\/00218"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The number of genes implicated in neurodevelopmental conditions is rapidly growing. Recently, variants in PPP2R1A have been associated with syndromic intellectual disability and a consistent, but still expanding, phenotype. The PPP2R1A gene encodes a protein subunit of the serine\/threonine protein phosphatase 2A enzyme, which plays a critical role in cellular function. We report an individual showing pontocerebellar hypoplasia (PCH), microcephaly, optic and peripheral nerve abnormalities, and an absence of typical features like epilepsy and an abnormal corpus callosum. He bears an unreported variant in an atypical region of PPP2R1A. In silico studies, functional analysis using immunofluorescence, and super-resolution microscopy techniques were performed to investigate the pathogenicity of the variant. This analysis involved a comparative analysis of the patient\u2019s fibroblasts with both healthy control cells and cells from an individual with the previously described phenotype. The results showed reduced expression of PPP2R1A and the presence of aberrant protein aggregates in the patient\u2019s fibroblasts, supporting the pathogenicity of the variant. These findings suggest a potential association between PPP2R1A variants and PCH, expanding the clinical spectrum of PPP2R1A-related neurodevelopmental disorder. Further studies and descriptions of additional patients are needed to fully understand the genotype\u2013phenotype correlation and the underlying mechanisms of this novel phenotype.<\/jats:p>","DOI":"10.3390\/ijms241813699","type":"journal-article","created":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T09:46:20Z","timestamp":1693907180000},"page":"13699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Advanced Optical Microscopy: Unveiling Functional Insights Regarding a Novel PPP2R1A Variant and Its Unreported Phenotype"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9530-6234","authenticated-orcid":false,"given":"M\u00f2nica","family":"Rold\u00e1n","sequence":"first","affiliation":[{"name":"Confocal Microscopy and Cellular Imaging Unit, Genetic and Molecular Medicine Department, Pediatric Institute for Rare Diseases, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-4793","authenticated-orcid":false,"given":"Gregorio Alexander","family":"Nolasco","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Pediatric Neurology Department, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Llu\u00eds","family":"Armengol","sequence":"additional","affiliation":[{"name":"Quantitative Genomic Medicine Laboratories, qGenomics, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos","family":"Fr\u00edas","sequence":"additional","affiliation":[{"name":"Confocal Microscopy and Cellular Imaging Unit, Genetic and Molecular Medicine Department, Pediatric Institute for Rare Diseases, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Morell","sequence":"additional","affiliation":[{"name":"Quantitative Genomic Medicine Laboratories, qGenomics, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manel","family":"Garc\u00eda-Aragon\u00e9s","sequence":"additional","affiliation":[{"name":"Quantitative Genomic Medicine Laboratories, qGenomics, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florencia","family":"Epifani","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Pediatric Neurology Department, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Muchart","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Diagnostic Imaging Department, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Luisa","family":"Ram\u00edrez-Almaraz","sequence":"additional","affiliation":[{"name":"Genetic and Molecular Medicine Department, Pediatric Institute for Rare Diseases, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0898-7332","authenticated-orcid":false,"given":"Loreto","family":"Martorell","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Genetic and Molecular Medicine Department, Pediatric Institute for Rare Diseases, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5811-134X","authenticated-orcid":false,"given":"Cristina","family":"Hernando-Davalillo","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Genetic and Molecular Medicine Department, Pediatric Institute for Rare Diseases, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3617-7134","authenticated-orcid":false,"given":"Roser","family":"Urreizti","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBER-ER), Instituto de Salud Carlos III, 28220 Barcelona, Spain"},{"name":"Clinical Biochemistry Department, Hospital Sant Joan de Deu, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2056-2428","authenticated-orcid":false,"given":"Mercedes","family":"Serrano","sequence":"additional","affiliation":[{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Pediatric Neurology Department, Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBER-ER), Instituto de Salud Carlos III, 28220 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1172\/JCI79860","article-title":"B56\u03b4-related protein phosphatase 2A dysfunction identified in patients with intellectual disability","volume":"125","author":"Houge","year":"2015","journal-title":"J. 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