A case of CADASIL caused by NOTCH3 c.512_605delinsA heterozygous mutation.

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.