Characteristics of CADASIL in Korea - A novel cysteine-sparing Notch3 mutation

Objective: To elucidate the phenotype, genotype, and MRI findings of Korean patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ( CADASIL) and mutation carriers. Methods: The authors studied 40 members of nine unrelated Korean CADASIL families. After genetic analysis of Notch3, clinical and MRI findings were correlated in 27 mutation carriers. Result: Notch3 mutation sites were C174R ( one family, n = 3), R133C ( one family, n = 3), R587C ( one family, n = 1), R544C (two families, n = 5), and R75P ( four families, n = 15). The clinical features were typical of CADASIL, but the frequency of migraine in the Korean population appears low. MRI abnormalities were found in 54% of the mutant carriers, the most common being white matter hyperintensities. The prevalence of lacunes and microbleeds increased with patient age. Anterior temporal areas were less often involved in subjects with R75P mutations than in those where mutations occurred in other sites ( p = 0.02). Gradient echo imaging identified microbleedings in 33% of mutation carriers (64% of those with abnormal MRI), whereas diffusion-weighted MRI showed abnormal findings in only one patient. Neurologic disability was related to the number of lacunar infarcts and the lesion volume of white matter hyperintensities (p < 0.001) whereas MMSE score was related to the number of lacunar infarcts (p < 0.005). Conclusions: Although Korean cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy ( CADASIL) mutation carriers show similar clinical and MRI findings, these abnormalities appear less frequently than in other populations. Relatively frequent microbleedings on gradient echo imaging suggest that treatment should be individualized according to MRI findings. The novel mutation of R75P, not involving a cysteine residue, is related to less frequent involvement of the anterior temporal area, thus broadening the spectrum of CADASIL.