Detecting a Novel <i>NOTCH3</i> Variant in Patients with Suspected CADASIL: A Single Center Study

Abstract

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of familial cerebral small vessel disease in adults and is caused by &lt;i&gt;NOTCH3&lt;/i&gt; variants. Clinical manifestations of CADASIL include recurrent ischemic strokes, dementia, migraine or migraineous headaches, epileptic seizures, and psychiatric disorders. The clinical-radiological phenotype of the disease is also highly variable. In this study, we investigated the variability of clinical, radiological, and genetic data in patients analyzed for &lt;i&gt;NOTCH3&lt;/i&gt; variant in our clinic. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We performed clinical and neuropsychological examination, cerebral magnetic resonance imaging (MRI) and Doppler sonography of cerebral arteries in all patients. Next-generation sequencing test was used for detect variants in &lt;i&gt;NOTCH3&lt;/i&gt; gene from all CADASIL patients. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; By using the next-generation sequencing method, heterozygous c.380C&amp;gt;T pathogenic variant was detected in the 4th exon of the &lt;i&gt;NOTCH3&lt;/i&gt; gene in 3 patients. This is a previously unreported novel variant and resulted in the replacement of the amino acid Proline at 127th position with Leucine. &lt;b&gt;&lt;i&gt;Discussion and Conclusion:&lt;/i&gt;&lt;/b&gt; The discovery of this novel pathogenic variant region may contribute to the expansion of the clinical and genetic spectrum of diseases associated with NOTCH3, leading to further research and treatment options for this disease in the future.