Exon 4 Mutations Determination in NOTCH3 Gene for Cryptogenic Ischemic Stroke

Background: Ischemic stroke in young adults is often classified as cryptogenic (CIS) despite extensive investigation into potential causes. Genetic factors, including mutations in the NOTCH3 gene, are implicated in cerebrovascular diseases such as CADASIL. This study aimed to assess the clinical presentation, vascular risk factors (VRFs), and genetic contributions to CIS in young Algerian adults. Methods: A cross-sectional study was conducted with 42 CIS patients (aged ≤50 years), diagnosed based on the TOAST classification. Data on lifestyle-related VRFs, such as tobacco use and substance consumption, were obtained via interviews. Genotyping was performed on ten single nucleotide polymorphisms (SNPs) in exon 4 of the NOTCH3 gene, a region commonly associated with CADASIL mutations. Results: The mean age of participants was 38.31 ± 8.51 years, with a significant gender difference in age (P = 0.021). Tobacco consumption was a notable risk factor (P = 0.002). However, no mutations were detected in the targeted SNPs of exon 4 of the NOTCH3 gene, either in heterozygous or homozygous states. Conclusion: This suggests that mutations in exon 4 of the NOTCH3 gene may not be involved in the pathogenesis of CIS in this cohort or that unique genetic variants may exist in the Algerian population. The absence of mutations in the analyzed region underlines the need for further research, including comprehensive genetic analysis targeting the entire coding region of the NOTCH3 gene. Larger studies are essential to validate these findings and improve diagnostic, therapeutic, and preventive strategies for CIS in young adults.