Cerebral Small Vessel Disease
Cerebral small vessel disease (SVD) causes 20% of ischaemic stroke (lacunar stroke). It results from disease in the small perforating end arteries supplying the white matter and deep grey matter. This causes both small regions of infarction (lacunar infarcts) and more diffuse regions of ischaemia (leukoariosis). Both pathologies contribute to the cognitive impairment seen in the disease; it is the most common pathology causing vascular dementia.
Although most cases of SVD are sporadic with hypertension being the major risk factor, SVD is also the stroke phenotype which most commonly presents as a familial disorder. The most common monogenic form of stroke is a type of SVD (CADASIL “Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy”). Recently a number of other monogenic causes of SVD have been described including both recessive and dominant mutations.
There have also been multiple families described with autosomal recessive and dominant early onset SVD in whom no mutations in known genes have been identified. It is likely therefore that there are other, as yet undiscovered, monogenic forms of SVD. This project will utilise samples from patients with suspected monogenic SVD. To maximise efficiency we will apply a two stage process. In the first stage we will pre-screen for known genetic causes of SVD using a targeted next generation sequencing (NGS) platform approach. In the second phase we will perform whole genome sequencing in those cases in which mutations in known genes have been excluded.
Centres at which CSVD is currently recruiting
Cambridge University Hospitals NHS Foundation Trust
Kings College Hospital NHS Foundation Trust, London
Leeds University Hospital
NHS Greater Glasgow and Clyde
Oxford University NHS Foundation Trust
Royal Devon & Exeter NHS Foundation Trust
Sheffield Teaching Hospitals NHS Foundation Trust
St George’s Healthcare NHS Trust
University College London Hospital