Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784785711867625472
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
work_keys_str_mv AT arnedomaria molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT ascasoangela molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT latorrepellicerana molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT luciacamposcristina molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT gilsalvadormarta molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT ayerzacasasariadna molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT pablomariajesus molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT gomezpuertaspaulino molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT ramosfelicianoj molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT buenolozanogloria molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT piejuan molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches
AT puisacbeatriz molecularbasisoftheschuurshoeijmakerssyndromewhatweknowaboutthegeneandthepacs1proteinandnoveltherapeuticapproaches