Progressive Supranuclear Palsy (PSP) is a tauopathy characterized by progressive postural instability, vertical supranuclear gaze palsy, and cognitive impairment. Genetic studies have identified strong associations between PSP and variants in the MAPT (microtubule-associated protein tau) gene, particularly the H1 haplotype, which accounts for a significant portion of genetic risk. Specific pathogenic mutations in MAPT also cause familial PSP. [1]
PSP is a 4-repeat tauopathy with the following genetic architecture: [2]
The MAPT gene has two major haplotypes, H1 and H2. The H1 haplotype is overrepresented in PSP patients: [3]
The H1 haplotype contains several single nucleotide polymorphisms (SNPs) that tag the risk allele: [4]
The P301L mutation in MAPT is one of the most common pathogenic mutations causing familial PSP: [5]
This mutation affects tau exon 10 splicing:[^6]
Genome-wide association studies (GWAS) have identified STX6 as a risk gene for PSP:[^8]
MOBP variants are associated with PSP risk:[^9]
Variants in EIF2AK3, encoding the PERK protein involved in the unfolded protein response:[^10]
The genetic variants in MAPT lead to tau dysfunction:[11][12]
The H1 haplotype likely increases risk through:[2:1][3:1]
Genetic testing for PSP is considered in:[^13]
Testing typically includes:
The study of Psp Genetic Variants has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Use this navigation hub to connect disease phenotype, biomarkers, mechanisms, and intervention evidence for corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP).
This section highlights recent publications relevant to this disease.
Eating Disorders and Parkinson's Disease - 2: Population Burden, Genetic Epidemiology and Shared Genomics. ↩︎
SpikeID: Rapid and unbiased identification of SARS-CoV-2 variants by spike sequencing. ↩︎ ↩︎
Genome-wide association study of REM sleep behavior disorder in Parkinson's disease. ↩︎
Acetylation Mimetic and Null Mutations Within the Filament Core of P301L Tau Have Varied Effects on Susceptibility to Seeding and Aggregation. ↩︎