Mutational Screening of NOTCH3 Gene Reveals Two Novel Mutations: Complexity of CADASIL Diagnosis.

[cadasil]

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL ) is an adult onset hereditary vascular disease with neurological manifestations . The classical clinical course is relentlessly progressive with early transient ischaemic attacks (TIA ) or strokes , dementia and finally death in the mid-1960 s . The disorder is inherited in an autosomal dominant fashion , with high penetrance and broad variable clinical course even within family . It is caused by mutations in the NOTCH 3 gene ; all causative mutations result in gain or loss of a cysteine residue within the extracellular domain , with exons 3 and 4 reported as hot spot mutational sites . Mutation analysis of the NOTCH 3 gene was performed through direct sequencing of the 2 -23 exons containing all EGF -like domains . Patients underwent genetic counselling pre and post testing . Here , we report two novel mutations located in exons 6 and 15 of the NOTCH 3 gene ; clinical description for the probands and for available relatives is enclosed . No reliable data on incidence or prevalence rates of this disease are available : it is therefore essential that the diagnosis is obtained in all suspected cases through the extensive analysis of the NOTCH 3 gene and that all cases are brought to the attention of the scientific community .