Abstract:

Objective   To analyse the NOTCH3 mutation of patients in a large Chinese family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL), and to discuss the application of mutation detection in the screening and diagnosis of genetic disease CADASIL. Methods   Peripheral blood of 8 individuals (5 patients with CADASIL, 3 normal individuals) was collected and the genomic DNA was extracted. Polymerase chain reaction (PCR) was performed for the hot spot mutation region amplification of NOTCH3. Direct DNA sequencing was used to find the pathologic mutation of the family with CADASIL. Results   A heterozygous missense mutation in exon 4 of NOTCH3 gene（c.421C＞T）was found, causing arginine at 141 position replaced by cysteine. The patients with CADASIL all carried this mutation, whereas the normal individuals did not. Conclusion   The heterozygous missense mutation（c.421C＞T） is co-segregation with the phenotype of the individuals with CADASIL in the Chinese family, which is the disease-causing mutation for the family.

Key words: CADASIL; Gene, NOTCH3; Point mutation; Gene diagnosis； Cerebrovascular accident