Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Associated With a Novel In-Frame Mutation in the NOTCH3 Gene in a Japanese Patient

Here, we report a case involving a 67-year-old Japanese woman with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) associated with a novel in-frame complex rearrangement in the NOTCH3 gene. The patient had gradually developed cognitive impairment since the occurrence of an ischemic stroke at the age of 53 years. Her mother had a history of stroke and dementia. Fluid-attenuated inversion recovery magnetic resonance imaging of the brain showed hyperintense lesions in the bilateral temporal poles, external capsules, and periventricular white matter accompanied by multiple cerebral microbleeds on T2*-weighted gradient-echo imaging. A novel in-frame mutation (c.598_610delinsAGAACCC) resulting in the loss of Cys201 in the fifth epidermal growth factor-like repeat of NOTCH3 was identified; this led to a diagnosis of CADASIL. In summary, we report a novel pathogenic mutation (NOTCH3 c.598_610delinsAGAACCC; p.Pro200_Ser204delinsArgThrPro) associated with CADASIL. Further investigations should elucidate the genotype-phenotype correlations in patients with this in-frame complex rearrangement.