Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL): first description of a Russian family with the identified mutation in the Notch3 gene

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described familial form of ischemic stroke caused by mutations in the Notch3 gene on chromosome 19q12. Clinically, CADASIL develops as a cerebrovascular small vessel disease: against a background of repeated lacunar strokes, progressing are subcortical, pseudobulbar and cerebellar syndromes and cognitive decline. Neuroimaging methods (CT, MRI) reveal combination of small lacunar infarcts of variable location withdiffuse white matter changes (leucoaraosis). In this paper we present the first description of a Russian family with the verified mutation in the Notch3 gene, nucleotide change 832GA in exon 5 leading to substitution of valine to methionine (Val252Met) at protein codon 252. This missense mutation is novel and has not been reported before in other families with CADASIL syndrome. The observation presented confirms that CADASIL syndrome should be suspected in all cases of white matter disease of unknown origin.

Keywords

• cadasil
• leukoencephalopathy
• notch3
• mutation screening