STXBP2 and progressive multifocal leukoencephalopathy: All four PML cases with the same STXBP2 variant were heterozygous (Supplementary Table 1) and in a comparison of natalizumab-treated multiple sclerosis (MS) patients who developed PML (n = 2/86) versus matched controls (natalizumab-treated MS patients who did not develop PML, n = 0/604) there was a 36-fold increased risk of PML (observed positive predictive value of 100%) (6).