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Molecular Basis of the Schuurs–Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches
The Schuurs–Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopment Disorder (PACS1-NDD) is a rare autosomal dominant disease caused by mutations in the PACS1 gene. To date, only 87 patients have been reported and, surprisingly, most of them carry the same variant (c.607C>T; p.R203W). The most rele...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456036/ https://www.ncbi.nlm.nih.gov/pubmed/36077045 http://dx.doi.org/10.3390/ijms23179649 |
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author | Arnedo, María Ascaso, Ángela Latorre-Pellicer, Ana Lucia-Campos, Cristina Gil-Salvador, Marta Ayerza-Casas, Ariadna Pablo, María Jesús Gómez-Puertas, Paulino Ramos, Feliciano J. Bueno-Lozano, Gloria Pié, Juan Puisac, Beatriz |
author_facet | Arnedo, María Ascaso, Ángela Latorre-Pellicer, Ana Lucia-Campos, Cristina Gil-Salvador, Marta Ayerza-Casas, Ariadna Pablo, María Jesús Gómez-Puertas, Paulino Ramos, Feliciano J. Bueno-Lozano, Gloria Pié, Juan Puisac, Beatriz |
author_sort | Arnedo, María |
collection | PubMed |
description | The Schuurs–Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopment Disorder (PACS1-NDD) is a rare autosomal dominant disease caused by mutations in the PACS1 gene. To date, only 87 patients have been reported and, surprisingly, most of them carry the same variant (c.607C>T; p.R203W). The most relevant clinical features of the syndrome include neurodevelopment delay, seizures or a recognizable facial phenotype. Moreover, some of these characteristics overlap with other syndromes, such as the PACS2 or Wdr37 syndromes. The encoded protein phosphofurin acid cluster sorting 1 (PACS-1) is able to bind to different client proteins and direct them to their subcellular final locations. Therefore, although its main function is protein trafficking, it could perform other roles related to its client proteins. In patients with PACS1-NDD, a gain-of-function or a dominant negative mechanism for the mutated protein has been suggested. This, together with the fact that most of the patients carry the same genetic variant, makes it a good candidate for novel therapeutic approaches directed to decreasing the toxic effect of the mutated protein. Some of these strategies include the use of antisense oligonucleotides (ASOs) or targeting of its client proteins. |
format | Online Article Text |
id | pubmed-9456036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94560362022-09-09 Molecular Basis of the Schuurs–Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches Arnedo, María Ascaso, Ángela Latorre-Pellicer, Ana Lucia-Campos, Cristina Gil-Salvador, Marta Ayerza-Casas, Ariadna Pablo, María Jesús Gómez-Puertas, Paulino Ramos, Feliciano J. Bueno-Lozano, Gloria Pié, Juan Puisac, Beatriz Int J Mol Sci Review The Schuurs–Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopment Disorder (PACS1-NDD) is a rare autosomal dominant disease caused by mutations in the PACS1 gene. To date, only 87 patients have been reported and, surprisingly, most of them carry the same variant (c.607C>T; p.R203W). The most relevant clinical features of the syndrome include neurodevelopment delay, seizures or a recognizable facial phenotype. Moreover, some of these characteristics overlap with other syndromes, such as the PACS2 or Wdr37 syndromes. The encoded protein phosphofurin acid cluster sorting 1 (PACS-1) is able to bind to different client proteins and direct them to their subcellular final locations. Therefore, although its main function is protein trafficking, it could perform other roles related to its client proteins. In patients with PACS1-NDD, a gain-of-function or a dominant negative mechanism for the mutated protein has been suggested. This, together with the fact that most of the patients carry the same genetic variant, makes it a good candidate for novel therapeutic approaches directed to decreasing the toxic effect of the mutated protein. Some of these strategies include the use of antisense oligonucleotides (ASOs) or targeting of its client proteins. MDPI 2022-08-25 /pmc/articles/PMC9456036/ /pubmed/36077045 http://dx.doi.org/10.3390/ijms23179649 Text en © 2022 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 | Review Arnedo, María Ascaso, Ángela Latorre-Pellicer, Ana Lucia-Campos, Cristina Gil-Salvador, Marta Ayerza-Casas, Ariadna Pablo, María Jesús Gómez-Puertas, Paulino Ramos, Feliciano J. Bueno-Lozano, Gloria Pié, Juan Puisac, Beatriz Molecular Basis of the Schuurs–Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches |
title | Molecular Basis of the Schuurs–Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches |
title_full | Molecular Basis of the Schuurs–Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches |
title_fullStr | Molecular Basis of the Schuurs–Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches |
title_full_unstemmed | Molecular Basis of the Schuurs–Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches |
title_short | Molecular Basis of the Schuurs–Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches |
title_sort | molecular basis of the schuurs–hoeijmakers syndrome: what we know about the gene and the pacs-1 protein and novel therapeutic approaches |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456036/ https://www.ncbi.nlm.nih.gov/pubmed/36077045 http://dx.doi.org/10.3390/ijms23179649 |
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