Interestingly, despite an overall effect of higher-numbered EGFr domains being associated with a milder phenotype, we found that PV in EGFr domains 10 and 11, which comprise the ligand-binding domain and lead to reduced NOTCH3 signalling,21–24 are associated with a higher WMH lesion load when compared with all other EGFr domains. This evidence concerns the gene EGFR and acquired polycythemia vera.