Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kim, Yerim, Bae, Jong Seok, Lee, Ju-Young, Song, Hong Ki, Lee, Ju-Hun, Lee, Minwoo, Kim, Chulho, Lee, Sang-Hwa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784809929750609920
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
work_keys_str_mv AT kimyerim genotypeandphenotypedifferencesincadasilfromanasianperspective
AT baejongseok genotypeandphenotypedifferencesincadasilfromanasianperspective
AT leejuyoung genotypeandphenotypedifferencesincadasilfromanasianperspective
AT songhongki genotypeandphenotypedifferencesincadasilfromanasianperspective
AT leejuhun genotypeandphenotypedifferencesincadasilfromanasianperspective
AT leeminwoo genotypeandphenotypedifferencesincadasilfromanasianperspective
AT kimchulho genotypeandphenotypedifferencesincadasilfromanasianperspective
AT leesanghwa genotypeandphenotypedifferencesincadasilfromanasianperspective