It is plausible that the protective H2 haplotype exerts an epistatic effect on its opposing mutant allele. Therefore, our findings raise the possibility that underlying genetic factors play a role in influencing the functional effect of the 10+16 mutation on MAPT exon 10 splicing and affect expressivity and cellular and clinicopathological phenotype, as described in other tauopathies.3, 15. The gene discussed is MAPT; the disease is tauopathy.