Even though the proportion of nonsynonymous variants in the exon 5 cytoplasmic region did not differ significantly between EA ND cases and comparison subjects, we identified a missense rare variant, p.Pro451Leu, that was significantly more frequent in controls and may have a protective effect with respect to ND risk in that population. p.Pro451Leu is predicted by PolyPhen to be damaging, and was exclusively observed in EA subjects. In the discovery sample, this variant was found in 3 controls and 1 case; in the test sample, it was observed in 5 comparison subjects and 1 case. The difference is marginally significant (FET p=0.05).
