CEREBRAL AUTOSOMAL DOMINANT ARTERIOPATHY WITH SUBCORTICAL INFARCTS AND LEUKOENCEPHALOPATHY (CADASIL)

NOTCH3 GENE ANALYSIS IN CADASIL

CADASIL is an autosomal dominantly inherited disorder characterised by five main symptoms, migraine with aura, subcortical ischaemic events, mood disturbances, apathy and cognitive impairment. These symptoms vary in frequency with age and duration of disease (Chabriat et al. 2009 Lancet Neurol 8(7):643-653). Germline variants in exons 3-24 of the NOTCH3 gene are found in approximately 90% of patients with a diagnosis of CADASIL. The NOTCH3 gene contains 33 exons, with exons 3-24 coding for Epidermal growth factor (EGF) like repeats which are involved in ligand binding. Sequencing of exons 3 and 4 will identify disease-causing variants in approximately 65% of patients with CADASIL (Joutel et al. 1997 Lancet 350,:1511-1515). All patients will be screened for variants in exons 3 and 4.  Only patients fulfilling the following criteria (1) typical white matter changes on MRI or (2) typical findings on skin biopsy or (3) positive family history consistent with a diagnosis of CADASIL, will be screened for exons 5-24.

The laboratory participates in the European Molecular Genetics Quality Network (EMQN) sequencing scheme.