Novel NOTCH3 mutation c.1564 T > A (p.Cys522Ser) presenting with early-onset Parkinsonism and white matter lesions

Abstract

CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a hereditary small vessel disease caused by mutations in the NOTCH3 gene, characterized by recurrent strokes, cognitive decline, and psychiatric symptoms. This report presents a novel NOTCH3 c.1564 T > A (p.Cys522Ser) mutation associated with early-onset parkinsonism and significant white matter lesions. We describe a patient who presented with early-onset parkinsonism, characterized by bradykinesia and rigidity, alongside extensive white matter lesions observed through neuroimaging. Genetic testing revealed a novel c.1564 T > A (p.Cys522Ser) mutation in the NOTCH3 gene, contributing to the clinical diagnosis of CADASIL. This case underscores the phenotypic variability of CADASIL and the potential for atypical presentations, including parkinsonism. Early identification of genetic mutations can facilitate appropriate management and counseling for affected individuals and their families. Further research is warranted to explore the mechanisms underlying the association between NOTCH3 mutations and parkinsonism. Our findings contribute to the understanding of CADASIL, suggesting that clinicians should consider CADASIL in differential diagnoses of early-onset parkinsonism, especially in patients with concurrent white matter lesions.