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Advanced Optical Microscopy: Unveiling Functional Insights Regarding a Novel PPP2R1A Variant and Its Unreported Phenotype

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 p...

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Autores principales: Roldán, Mònica, Nolasco, Gregorio Alexander, Armengol, Lluís, Frías, Marcos, Morell, Marta, García-Aragonés, Manel, Epifani, Florencia, Muchart, Jordi, Ramírez-Almaraz, María Luisa, Martorell, Loreto, Hernando-Davalillo, Cristina, Urreizti, Roser, Serrano, Mercedes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530954/
https://www.ncbi.nlm.nih.gov/pubmed/37762002
http://dx.doi.org/10.3390/ijms241813699
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author Roldán, Mònica
Nolasco, Gregorio Alexander
Armengol, Lluís
Frías, Marcos
Morell, Marta
García-Aragonés, Manel
Epifani, Florencia
Muchart, Jordi
Ramírez-Almaraz, María Luisa
Martorell, Loreto
Hernando-Davalillo, Cristina
Urreizti, Roser
Serrano, Mercedes
author_facet Roldán, Mònica
Nolasco, Gregorio Alexander
Armengol, Lluís
Frías, Marcos
Morell, Marta
García-Aragonés, Manel
Epifani, Florencia
Muchart, Jordi
Ramírez-Almaraz, María Luisa
Martorell, Loreto
Hernando-Davalillo, Cristina
Urreizti, Roser
Serrano, Mercedes
author_sort Roldán, Mònica
collection PubMed
description 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’s 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’s 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–phenotype correlation and the underlying mechanisms of this novel phenotype.
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spelling pubmed-105309542023-09-28 Advanced Optical Microscopy: Unveiling Functional Insights Regarding a Novel PPP2R1A Variant and Its Unreported Phenotype Roldán, Mònica Nolasco, Gregorio Alexander Armengol, Lluís Frías, Marcos Morell, Marta García-Aragonés, Manel Epifani, Florencia Muchart, Jordi Ramírez-Almaraz, María Luisa Martorell, Loreto Hernando-Davalillo, Cristina Urreizti, Roser Serrano, Mercedes Int J Mol Sci Article 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’s 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’s 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–phenotype correlation and the underlying mechanisms of this novel phenotype. MDPI 2023-09-05 /pmc/articles/PMC10530954/ /pubmed/37762002 http://dx.doi.org/10.3390/ijms241813699 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Roldán, Mònica
Nolasco, Gregorio Alexander
Armengol, Lluís
Frías, Marcos
Morell, Marta
García-Aragonés, Manel
Epifani, Florencia
Muchart, Jordi
Ramírez-Almaraz, María Luisa
Martorell, Loreto
Hernando-Davalillo, Cristina
Urreizti, Roser
Serrano, Mercedes
Advanced Optical Microscopy: Unveiling Functional Insights Regarding a Novel PPP2R1A Variant and Its Unreported Phenotype
title Advanced Optical Microscopy: Unveiling Functional Insights Regarding a Novel PPP2R1A Variant and Its Unreported Phenotype
title_full Advanced Optical Microscopy: Unveiling Functional Insights Regarding a Novel PPP2R1A Variant and Its Unreported Phenotype
title_fullStr Advanced Optical Microscopy: Unveiling Functional Insights Regarding a Novel PPP2R1A Variant and Its Unreported Phenotype
title_full_unstemmed Advanced Optical Microscopy: Unveiling Functional Insights Regarding a Novel PPP2R1A Variant and Its Unreported Phenotype
title_short Advanced Optical Microscopy: Unveiling Functional Insights Regarding a Novel PPP2R1A Variant and Its Unreported Phenotype
title_sort advanced optical microscopy: unveiling functional insights regarding a novel ppp2r1a variant and its unreported phenotype
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530954/
https://www.ncbi.nlm.nih.gov/pubmed/37762002
http://dx.doi.org/10.3390/ijms241813699
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