Reader response: NOTCH3 cysteine-altering variant is an important risk factor for stroke in the Taiwanese population
XingshunXu, Neurologist, Department of Neurology, the First Affiliated Hospital of Soochow University
MiaoSun, Genetic scientist, Institute of Fetology, the First Affiliated Hospital of Soochow University
Submitted January 11, 2020
Lee et al.1 reported that the p.R544C variant of NOTCH3 gene is a risk factor for stroke—especially small vessel occlusion subtype of stroke—in the Taiwan population. This is very interesting because a nearly 1% high frequency of the p.R544C variant was found in the Taiwan population due to the founder effect in Taiwan1, 2, but this mutation has a relative low global allele frequency of about 0.0001 from The Genome Aggregation Database. Since the p.R544C variant of NOTCH3 gene has been identified as a pathogenic mutation for CADASIL3, this results in a high incidence of CADASIL in Taiwan. In addition, the most common symptom of CADASIL is recurrent small vessel stroke in more than 50% of patients.4
Therefore, the authors may conclude that p.R544C variant-caused high incidence of CADASIL increased the ratio of CADASIL in stroke composition, rather than that the increase of the genotype frequency of p.R544C contributes the risk of stroke. According to authors’ logics in this article,1 this variant of NOTCH3 gene could be also a risk factor for dementia because dementia is another main symptom of CADASIL. The authors selected 550 stroke and dementia-free individuals as control subjects, which precluded part of CADASIL patients with dementia carrying the p.R544C variant in the controls and relatively overestimated p.R544C variant-caused stroke risk, thereby weakening their conclusion.
Disclosure
The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures.
References
Lee YC, Chung CP, Chang MH, Wang SJ, Liao YC. NOTCH3 cysteine-altering variant is an important risk factor for stroke in the Taiwanese population. Neurology 2020;94:e87–e96.
Lee YC, Liu CS, Chang MH, et al. Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese. J Neurol 2009;256:249–255.
Liao YC, Hsiao CT, Fuh JL, et al. Characterization of CADASIL among the Han Chinese in Taiwan: Distinct Genotypic and Phenotypic Profiles. PloS One 2015;10:e0136501.
Wang MM. Cadasil. Handb Clin Neurol 2018;148:733–743.
Lee et al.1 reported that the p.R544C variant of NOTCH3 gene is a risk factor for stroke—especially small vessel occlusion subtype of stroke—in the Taiwan population. This is very interesting because a nearly 1% high frequency of the p.R544C variant was found in the Taiwan population due to the founder effect in Taiwan1, 2, but this mutation has a relative low global allele frequency of about 0.0001 from The Genome Aggregation Database. Since the p.R544C variant of NOTCH3 gene has been identified as a pathogenic mutation for CADASIL3, this results in a high incidence of CADASIL in Taiwan. In addition, the most common symptom of CADASIL is recurrent small vessel stroke in more than 50% of patients.4
Therefore, the authors may conclude that p.R544C variant-caused high incidence of CADASIL increased the ratio of CADASIL in stroke composition, rather than that the increase of the genotype frequency of p.R544C contributes the risk of stroke. According to authors’ logics in this article,1 this variant of NOTCH3 gene could be also a risk factor for dementia because dementia is another main symptom of CADASIL. The authors selected 550 stroke and dementia-free individuals as control subjects, which precluded part of CADASIL patients with dementia carrying the p.R544C variant in the controls and relatively overestimated p.R544C variant-caused stroke risk, thereby weakening their conclusion.
Disclosure
The authors report no relevant disclosures. Contact journal@neurology.org for full disclosures.
References