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Genotype and Phenotype Differences in CADASIL from an Asian Perspective
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small-vessel disease caused by mutations in the NOTCH3 gene. Classical pathogenic mechanisms are associated with cysteine gain or loss, but recent studies suggest that cystei...
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/PMC9569740/ https://www.ncbi.nlm.nih.gov/pubmed/36232798 http://dx.doi.org/10.3390/ijms231911506 |
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author | Kim, Yerim Bae, Jong Seok Lee, Ju-Young Song, Hong Ki Lee, Ju-Hun Lee, Minwoo Kim, Chulho Lee, Sang-Hwa |
author_facet | Kim, Yerim Bae, Jong Seok Lee, Ju-Young Song, Hong Ki Lee, Ju-Hun Lee, Minwoo Kim, Chulho Lee, Sang-Hwa |
author_sort | Kim, Yerim |
collection | PubMed |
description | Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small-vessel disease caused by mutations in the NOTCH3 gene. Classical pathogenic mechanisms are associated with cysteine gain or loss, but recent studies suggest that cysteine-sparing mutations might have a potential role as a pathogen. In comparison with CADASIL patients in Western countries, there are several differences in Asian patients: (1) prevalent locus of NOTCH3 mutations (exons 2–6 [particularly exon 4] vs. exon 11), (2) age at symptom onset, (3) prevalence of cerebral microbleeds and hemorrhagic stroke, (4) clinical symptoms, and (5) severity of white matter hyperintensities and typical involvement of the anterior temporal pole in magnetic resonance imaging. Both ethnicity and founder effects contribute to these differences in the clinical NOTCH3 spectrum in different cohorts. More functional investigations from diverse races are needed to clarify unknown but novel variants of NOTCH3 mutations. This review may broaden the spectrum of NOTCH3 variants from an Asian perspective and draw attention to the hidden pathogenic roles of NOTCH3 variants. |
format | Online Article Text |
id | pubmed-9569740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95697402022-10-17 Genotype and Phenotype Differences in CADASIL from an Asian Perspective Kim, Yerim Bae, Jong Seok Lee, Ju-Young Song, Hong Ki Lee, Ju-Hun Lee, Minwoo Kim, Chulho Lee, Sang-Hwa Int J Mol Sci Review Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary cerebral small-vessel disease caused by mutations in the NOTCH3 gene. Classical pathogenic mechanisms are associated with cysteine gain or loss, but recent studies suggest that cysteine-sparing mutations might have a potential role as a pathogen. In comparison with CADASIL patients in Western countries, there are several differences in Asian patients: (1) prevalent locus of NOTCH3 mutations (exons 2–6 [particularly exon 4] vs. exon 11), (2) age at symptom onset, (3) prevalence of cerebral microbleeds and hemorrhagic stroke, (4) clinical symptoms, and (5) severity of white matter hyperintensities and typical involvement of the anterior temporal pole in magnetic resonance imaging. Both ethnicity and founder effects contribute to these differences in the clinical NOTCH3 spectrum in different cohorts. More functional investigations from diverse races are needed to clarify unknown but novel variants of NOTCH3 mutations. This review may broaden the spectrum of NOTCH3 variants from an Asian perspective and draw attention to the hidden pathogenic roles of NOTCH3 variants. MDPI 2022-09-29 /pmc/articles/PMC9569740/ /pubmed/36232798 http://dx.doi.org/10.3390/ijms231911506 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 Kim, Yerim Bae, Jong Seok Lee, Ju-Young Song, Hong Ki Lee, Ju-Hun Lee, Minwoo Kim, Chulho Lee, Sang-Hwa Genotype and Phenotype Differences in CADASIL from an Asian Perspective |
title | Genotype and Phenotype Differences in CADASIL from an Asian Perspective |
title_full | Genotype and Phenotype Differences in CADASIL from an Asian Perspective |
title_fullStr | Genotype and Phenotype Differences in CADASIL from an Asian Perspective |
title_full_unstemmed | Genotype and Phenotype Differences in CADASIL from an Asian Perspective |
title_short | Genotype and Phenotype Differences in CADASIL from an Asian Perspective |
title_sort | genotype and phenotype differences in cadasil from an asian perspective |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9569740/ https://www.ncbi.nlm.nih.gov/pubmed/36232798 http://dx.doi.org/10.3390/ijms231911506 |
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