Supranuclear Palsy, Progressive, 3


For a phenotypic description and a discussion of genetic heterogeneity of progressive supranuclear palsy (PSP), see PSNP1 (601104).


Using a pooling-based genomewide association study of more than 500,000 SNPs in 288 patients with PSP and 344 age- and sex-matched controls, Melquist et al. (2007) identified candidate SNPs with large differences in allelic frequency by ranking all SNPs by their probe-intensity difference between cohorts. The MAPT H1 haplotype (see 157140) was strongly detected by this approach as was a second major locus (PSNP3) on chromosome 11p12-p11 that showed evidence of association at allelic (p less than 0.001), genotypic (p less than 0.001), and haplotypic (p less than 0.0001) levels and was narrowed to a single haplotype block containing the DNA damage-binding protein-2 (DDB2; 600811) and lysosomal acid phosphatase-2 (ACP2; 171650) genes. Since DNA damage and lysosomal dysfunction have been implicated in aging and neurodegenerative processes, Melquist et al. (2007) considered both genes to be viable candidates for conferring risk of disease.