Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disorder caused by NOTCH3 mutations, usually localized to exons 3 and 4, and characterized by recurrent subcortical infarctions, dementia and leukoencephalopathy. So far, there has been only limited information about CADASIL in Chinese population.
Objectives: To analyze the NOTCH3 mutations in ethnic Chinese in Taiwan with clinically suspected CADASIL and to characterize their clinical and molecular features.
Methods: Mutation analysis of NOTCH3 by direct nucleotide sequencing was performed in eight unrelated Chinese patients with clinically suspected CADASIL. Skin biopsy with ultrastructural studies by electronic microscopy was performed in four patients.
Results: Five NOTCH3 mutations, S118C, R141C, R332C, R544C and C977S, respectively, were identified from five patients, of which S118C and C977S are novel. None of these nucleotide sequence variations could be found among 50 healthy controls. Among the five mutations, two were in exon 4, and the other three were in exons 6, 11 and 18, respectively. Skin biopsy showed the presence of characteristic granular osmiophilic material only in the patient with the NOTCH3 mutation of R332C.
Conclusion: Our study demonstrated the clinical and molecular features of CADASIL in Chinese patients and broadened the spectrum of NOTCH3 mutations. Lack of evidence of a strong clustering of mutations in a particular exon tentatively suggests that a comprehensive screening of NOTCH3 mutation is still necessary for molecular diagnosis of CADASIL in Chinese population.