Overview

Pathogenicity: Progressive Supranuclear Palsy : Pathogenic
Clinical Phenotype: Progressive Supranuclear Palsy
Position: (GRCh37/hg19):Chr17:44087706 A>C
dbSNP ID: NA
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Splicing Alteration
Expected Protein Consequence: Isoform Shift; Missense
Codon Change: AGC to CGC
Reference Isoform: Tau Isoform Tau-F (441 aa)
Genomic Region: Exon 10

Findings

This mutation was detected in a Japanese man with probable progressive supranuclear palsy (Ogaki et al., 2012). He had no family history of neurodegenerative disease and his healthy parents did not carry the mutation. Satellite testing confirmed paternity, therefore the mutation most likely occurred de novo in this individual. Symptom onset occurred at age 46, starting with difficulty speaking and breathing. He later developed dementia and motor symptoms including limb bradykinesia, gait disturbance, and frequent falling. Abnormal eye movements were also prominent from early in the disease course. He died at age 48.

Neuropathology

Unknown.

Biological Effect

In vitro this missense mutation affects exon 10 splicing, resulting in the overproduction of tau isoforms containing four microtubule binding repeat domains (4R tau) (Ogaki et al., 2012).

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References

Paper Citations

1. Ogaki K, Li Y, Takanashi M, Ishikawa KI, Kobayashi T, Nonaka T, Hasegawa M, Kishi M, Yoshino H, Funayama M, Tsukamoto T, Shioya K, Yokochi M, Imai H, Sasaki R, Kokubo Y, Kuzuhara S, Motoi Y, Tomiyama H, Hattori N. Analyses of the MAPT, PGRN, and C9orf72 mutations in Japanese patients with FTLD, PSP, and CBS. Parkinsonism Relat Disord. 2012 Jul 18; PubMed.

Further Reading

Learn More

1. Japanese Familial Alzheimer's Disease Database