The CADASIL Scale-J, A Modified Scale to Prioritize Access to Genetic Testing for Japanese CADASIL-Suspected Patients
| Autor: | Toshiki Mizuno, Ai Hamano, Tomoyuki Ohara, Ikuko Mizuta, Akiko Watanabe-Hosomi, Jun Matsuura, Mao Mukai, Takashi Koizumi |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male Pediatrics medicine.medical_specialty DNA Mutational Analysis CADASIL Health Services Accessibility Decision Support Techniques Leukoencephalopathy 03 medical and health sciences 0302 clinical medicine Asian People Japan Predictive Value of Tests Diabetes mellitus medicine Humans Genetic Predisposition to Disease Genetic Testing Family history Receptor Notch3 Stroke Aged Genetic testing Subcortical infarction medicine.diagnostic_test business.industry Rehabilitation Reproducibility of Results Middle Aged Pseudobulbar palsy medicine.disease Mutation Female Surgery Neurology (clinical) Cardiology and Cardiovascular Medicine business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Stroke and Cerebrovascular Diseases. 28:1431-1439 |
| ISSN: | 1052-3057 |
| DOI: | 10.1016/j.jstrokecerebrovasdis.2019.03.026 |
| Popis: | Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is definitely diagnosed by genetic testing. Such testing involves the analysis of exons 2-24 of NOTCH3, which encode the epidermal growth factor-like repeat domain, where CADASIL mutations are localized. We previously reported clinical diagnostic criteria for screening CADASIL-suspected Japanese patients prior to genetic testing. Because of its high sensitivity but low specificity, most patients need to undergo genetic testing. In this study, we aimed to develop the CADASIL scale-J, a modified scale to prioritize access to genetic testing for CADASIL-suspected Japanese patients. Methods: We modified the CADASIL scale reported by Pescini et al based on clinical features of 126 CADASIL patients and 53 NOTCH3-negative CADASIL-like patients diagnosed up until March 2016 (Phase 1). For validation, we recruited 69 consecutive patients for genetic testing of NOTCH3 from April 2016 to March 2017 (Phase 2). Results: We developed the CADASIL scale-J with a score ranging from 0 to 25 and the cut-off value of 16, using 8 items: hypertension, diabetes, young onset (≤50 years old), pseudobulbar palsy, stroke/TIA, family history, subcortical infarction, and temporal pole lesion. The sensitivity and specificity of the CADASIL scale-J were 78.9% and 85.7%, respectively. In Phase 2, we obtained a positive predictive value of 70.0% and a negative predictive value of 89.2%. In this study, we identified 54 mutations, 7 of which were novel. Conclusions: The CADASIL scale-J is helpful to prioritize access to genetic testing for CADASIL-suspected Japanese patients. |
| Databáze: | OpenAIRE |
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