Novel mutation of NOTCH3 gene in a Chinese Patient with CADASIL: A case report

Abstract

Introduction: 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. Case presentation: A 56-year-old woman was hospitalized due to migraines and recurrent cerebral infarction. Brain magnetic resonance imaging (MRI) showed multiple ischemic infarcts, microbleed lesions and demyelination of white matter around the bilateral ventricles. Mutation analysis identified a novel frameshift mutation, c.5171_5172delCA, p. (Thr1724fs17), in the NOTCH3 gene in a heterozygous state in this patient. Thus, this patient was diagnosed with genetically confirmed CADASIL. Conclusions We report a novel mutation, c.5171_5172delCA, p. (Thr1724fs17), in the NOTCH3 gene in a Chinese patient with CADASIL. This report broadens the NOTCH3 gene mutation spectrum.