Novel Characteristics of Race-Specific Genetic Functions in Korean CADASIL

<i>Background and Objectives:</i> Previous studies found differences in the characteristics of NOTCH3 mutations in Caucasians and Asians with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Therefore, we sought to investigate the corr...

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Main Authors: Yerim Kim, Seung-Hoon Lee
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Medicina
Subjects:
Online Access:https://www.mdpi.com/1010-660X/55/9/521
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spelling doaj-f4f2295855ee45189a45ba6de2708c5a2020-11-25T02:52:07ZengMDPI AGMedicina1010-660X2019-08-0155952110.3390/medicina55090521medicina55090521Novel Characteristics of Race-Specific Genetic Functions in Korean CADASILYerim Kim0Seung-Hoon Lee1Department of Neurology, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul 05355, KoreaThe Korean Cerebrovascular Research Institute, Seoul 03100, RKorea<i>Background and Objectives:</i> Previous studies found differences in the characteristics of NOTCH3 mutations in Caucasians and Asians with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Therefore, we sought to investigate the correlations between genetic and clinical/radiological findings in Korean CADASIL patients including some variants of unknown significance (VUS). <i>Materials and Methods:</i> We screened 198 patients with a suspected diagnosis of CADASIL between 2005 and 2015 via Sanger sequencing. <i>Results:</i> A total of 34 subjects (52.5 &#177; 9.5 years) were included. The majority of the mutations were in exon 3 and exon 11. R75P mutations (n = 5), followed by Y465C and R544C mutations (n = 4) were the most prevalent. Patients with those mutations exhibited less frequent anterior temporal (AT) or external capsular (EC) hyperintensities compared to patients with other locus mutations. Hemorrhagic stroke (HS) was found to be associated with mutations in exon 3 (R75P), exon 9 (Y465C), exon 11 (R587C), and exon 22 (R1175W variants), which were common locations in our study. Although it is unclear that genetic differences might affect the phenotypes in ethnicities, Asian population shows less migraine or seizure, but more intracerebral hemorrhage. Unlike in westernized countries, typical AT or EC hyperintensities may not be significant MRI markers, at least in Korean CADASIL patients. Furthermore, similar to R75P phenotypes, it is a novel finding that patients with Y465C and R1175W VUS have less frequent AT involvement than Caucasians. <i>Conclusion:</i> The associations between HS and common genetic locations account for the increased development of intracerebral hemorrhage in Koreans rather than Caucasians. We suggest that some CADASIL mutations appear to impart novel region-specific characteristics.https://www.mdpi.com/1010-660X/55/9/521CADASILmutationNOTCH 3 proteinstrokecerebral infarctionintracranial hemorrhage
collection DOAJ
language English
format Article
sources DOAJ
author Yerim Kim
Seung-Hoon Lee
spellingShingle Yerim Kim
Seung-Hoon Lee
Novel Characteristics of Race-Specific Genetic Functions in Korean CADASIL
Medicina
CADASIL
mutation
NOTCH 3 protein
stroke
cerebral infarction
intracranial hemorrhage
author_facet Yerim Kim
Seung-Hoon Lee
author_sort Yerim Kim
title Novel Characteristics of Race-Specific Genetic Functions in Korean CADASIL
title_short Novel Characteristics of Race-Specific Genetic Functions in Korean CADASIL
title_full Novel Characteristics of Race-Specific Genetic Functions in Korean CADASIL
title_fullStr Novel Characteristics of Race-Specific Genetic Functions in Korean CADASIL
title_full_unstemmed Novel Characteristics of Race-Specific Genetic Functions in Korean CADASIL
title_sort novel characteristics of race-specific genetic functions in korean cadasil
publisher MDPI AG
series Medicina
issn 1010-660X
publishDate 2019-08-01
description <i>Background and Objectives:</i> Previous studies found differences in the characteristics of NOTCH3 mutations in Caucasians and Asians with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Therefore, we sought to investigate the correlations between genetic and clinical/radiological findings in Korean CADASIL patients including some variants of unknown significance (VUS). <i>Materials and Methods:</i> We screened 198 patients with a suspected diagnosis of CADASIL between 2005 and 2015 via Sanger sequencing. <i>Results:</i> A total of 34 subjects (52.5 &#177; 9.5 years) were included. The majority of the mutations were in exon 3 and exon 11. R75P mutations (n = 5), followed by Y465C and R544C mutations (n = 4) were the most prevalent. Patients with those mutations exhibited less frequent anterior temporal (AT) or external capsular (EC) hyperintensities compared to patients with other locus mutations. Hemorrhagic stroke (HS) was found to be associated with mutations in exon 3 (R75P), exon 9 (Y465C), exon 11 (R587C), and exon 22 (R1175W variants), which were common locations in our study. Although it is unclear that genetic differences might affect the phenotypes in ethnicities, Asian population shows less migraine or seizure, but more intracerebral hemorrhage. Unlike in westernized countries, typical AT or EC hyperintensities may not be significant MRI markers, at least in Korean CADASIL patients. Furthermore, similar to R75P phenotypes, it is a novel finding that patients with Y465C and R1175W VUS have less frequent AT involvement than Caucasians. <i>Conclusion:</i> The associations between HS and common genetic locations account for the increased development of intracerebral hemorrhage in Koreans rather than Caucasians. We suggest that some CADASIL mutations appear to impart novel region-specific characteristics.
topic CADASIL
mutation
NOTCH 3 protein
stroke
cerebral infarction
intracranial hemorrhage
url https://www.mdpi.com/1010-660X/55/9/521
work_keys_str_mv AT yerimkim novelcharacteristicsofracespecificgeneticfunctionsinkoreancadasil
AT seunghoonlee novelcharacteristicsofracespecificgeneticfunctionsinkoreancadasil
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