Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic cerebral small-vessel disease characterized by migraine, recurrent ischemic strokes, psychiatric disorder, and progressive cognitive decline. CADASIL is a cerebrovascular disease closely related to the NOTCH3 gene and to date, over 300 mutations in this gene have been reported. Herein, we describe a patient with CADASIL carrying a novel NOTCH3 frameshift mutation in exon 28. We present the results of a detailed clinical work-up and, in the light of the published literature, discuss the pathophysiological relevance of this genetic finding. Objective To investigate the phenotypic features and causative gene in a Chinese patient with CADASIL. Material and Methods This is a multi-generation family with CADASIL. The brain computed tomography (CT) and magnetic resonance imaging (MRI) were performed for the proband and other affected family members. DNA samples were screened for gene mutation by whole exome sequencing (WES), and potential pathogenic mutations were validated by Sanger sequencing. Results One novel heterozygous frameshift mutation, c. 5171₅172delCA, p. (Thr1724fs17), in the NOTCH3 gene in a Chinese patient with CADASIL. Co-segregation analysis identified that the NOTCH3 mutation is the genetic cause. The patient presented with cerebellar ataxia. The brain MRI images presented atypical imaging features of CADASIL. Conclusions The novel pathogenic frameshift mutation, c. 5171₅172delCA, p. (Thr1724fs17), in the NOTCH3 gene causes CADASIL, which enlarges the mutational spectrum of NOTCH3.
Lin et al. (Mon,) studied this question.