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Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is caused by mutations in the NOTCH3 gene, affecting the number of cysteines in the extracellular domain of the receptor, causing protein misfolding and receptor aggregation. The pathogenic role of c...

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Autores principales: Muiño, Elena, Gallego-Fabrega, Cristina, Cullell, Natalia, Carrera, Caty, Torres, Nuria, Krupinski, Jurek, Roquer, Jaume, Montaner, Joan, Fernández-Cadenas, Israel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618613/
https://www.ncbi.nlm.nih.gov/pubmed/28902129
http://dx.doi.org/10.3390/ijms18091964
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author Muiño, Elena
Gallego-Fabrega, Cristina
Cullell, Natalia
Carrera, Caty
Torres, Nuria
Krupinski, Jurek
Roquer, Jaume
Montaner, Joan
Fernández-Cadenas, Israel
author_facet Muiño, Elena
Gallego-Fabrega, Cristina
Cullell, Natalia
Carrera, Caty
Torres, Nuria
Krupinski, Jurek
Roquer, Jaume
Montaner, Joan
Fernández-Cadenas, Israel
author_sort Muiño, Elena
collection PubMed
description CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is caused by mutations in the NOTCH3 gene, affecting the number of cysteines in the extracellular domain of the receptor, causing protein misfolding and receptor aggregation. The pathogenic role of cysteine-sparing NOTCH3 missense mutations in patients with typical clinical CADASIL syndrome is unknown. The aim of this article is to describe these mutations to clarify if any could be potentially pathogenic. Articles on cysteine-sparing NOTCH3 missense mutations in patients with clinical suspicion of CADASIL were reviewed. Mutations were considered potentially pathogenic if patients had: (a) typical clinical CADASIL syndrome; (b) diffuse white matter hyperintensities; (c) the 33 NOTCH3 exons analyzed; (d) mutations that were not polymorphisms; and (e) Granular osmiophilic material (GOM) deposits in the skin biopsy. Twenty-five different mutations were listed. Four fulfill the above criteria: p.R61W; p.R75P; p.D80G; and p.R213K. Patients carrying these mutations had typical clinical CADASIL syndrome and diffuse white matter hyperintensities, mostly without anterior temporal pole involvement. Cysteine-sparing NOTCH3 missense mutations are associated with typical clinical CADASIL syndrome and typical magnetic resonance imaging (MRI) findings, although with less involvement of the anterior temporal lobe. Hence, these mutations should be further studied to confirm their pathological role in CADASIL.
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spelling pubmed-56186132017-09-30 Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL Muiño, Elena Gallego-Fabrega, Cristina Cullell, Natalia Carrera, Caty Torres, Nuria Krupinski, Jurek Roquer, Jaume Montaner, Joan Fernández-Cadenas, Israel Int J Mol Sci Review CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is caused by mutations in the NOTCH3 gene, affecting the number of cysteines in the extracellular domain of the receptor, causing protein misfolding and receptor aggregation. The pathogenic role of cysteine-sparing NOTCH3 missense mutations in patients with typical clinical CADASIL syndrome is unknown. The aim of this article is to describe these mutations to clarify if any could be potentially pathogenic. Articles on cysteine-sparing NOTCH3 missense mutations in patients with clinical suspicion of CADASIL were reviewed. Mutations were considered potentially pathogenic if patients had: (a) typical clinical CADASIL syndrome; (b) diffuse white matter hyperintensities; (c) the 33 NOTCH3 exons analyzed; (d) mutations that were not polymorphisms; and (e) Granular osmiophilic material (GOM) deposits in the skin biopsy. Twenty-five different mutations were listed. Four fulfill the above criteria: p.R61W; p.R75P; p.D80G; and p.R213K. Patients carrying these mutations had typical clinical CADASIL syndrome and diffuse white matter hyperintensities, mostly without anterior temporal pole involvement. Cysteine-sparing NOTCH3 missense mutations are associated with typical clinical CADASIL syndrome and typical magnetic resonance imaging (MRI) findings, although with less involvement of the anterior temporal lobe. Hence, these mutations should be further studied to confirm their pathological role in CADASIL. MDPI 2017-09-13 /pmc/articles/PMC5618613/ /pubmed/28902129 http://dx.doi.org/10.3390/ijms18091964 Text en © 2017 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Muiño, Elena
Gallego-Fabrega, Cristina
Cullell, Natalia
Carrera, Caty
Torres, Nuria
Krupinski, Jurek
Roquer, Jaume
Montaner, Joan
Fernández-Cadenas, Israel
Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL
title Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL
title_full Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL
title_fullStr Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL
title_full_unstemmed Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL
title_short Systematic Review of Cysteine-Sparing NOTCH3 Missense Mutations in Patients with Clinical Suspicion of CADASIL
title_sort systematic review of cysteine-sparing notch3 missense mutations in patients with clinical suspicion of cadasil
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618613/
https://www.ncbi.nlm.nih.gov/pubmed/28902129
http://dx.doi.org/10.3390/ijms18091964
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