Related Experiment Video
Updated: Oct 19, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
A case of CADASIL caused by NOTCH3 c.512_605delinsA heterozygous mutation
Jiahui Liu1, Qiaoyu Zhang1, Qi Wang1
1Department of Neurology, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Insights
Researchers identified a new NOTCH3 gene mutation, c.512_605delinsA, in a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This finding advances genetic diagnosis and targeted treatment for this rare cerebrovascular disorder.
Area of Science:
- Genetics
- Neurology
- Molecular Biology
Background:
- Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disorder.
- The NOTCH3 gene is strongly associated with CADASIL, with over 200 identified mutations.
Observation:
- Whole-exome sequencing (WES) was employed to screen the NOTCH3 gene in a CADASIL patient.
- Suspicious mutation sites identified by WES were confirmed using PCR amplification and Sanger sequencing.
Findings:
- A novel heterozygous deletion-insertion mutation, c.512_605delinsA, was detected in exon 4 of the NOTCH3 gene.
- This mutation results in amino acid alterations (p.G171_A202delinsE) and is considered a potential clinical variant for CADASIL.
Implications:
- The identification of this specific NOTCH3 mutation provides a crucial foundation for genotype-specific diagnosis of CADASIL.
- This discovery supports the development of targeted gene-based therapeutic strategies for patients with CADASIL.
Background:
Autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebrovascular disease closely related to the NOTCH3 gene. More than 200 mutations in this gene have been reported to be associated with this disease.
Methods:
The NOTCH3 gene from CADASIL patient was screened for mutations by whole-exome sequencing (WES). PCR amplification and direct Sanger sequencing were used to verify the suspicious gene mutation sites detected by WES.
Results:
We performed second-generation sequencing on a sample of the patient's genome and found a heterozygous deletion-insertion mutation c.512_605delinsA in exon 4 of NOTCH3, which resulted in amino acid changes p.G171_A202delinsE. This variation was confirmed by the direct Sanger sequencing. It may be rated as a CADASIL clinical variation.
Conclusion:
Discovery of this mutation site provides an important theoretical basis for specific gene-based diagnosis and treatment of CADASIL.
Related Concept Videos
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
02:26Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
01:43Incomplete Dominance
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:25Structure of Cadherins