Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11.

Abstract

The microtubule-associated protein tau (encoded by MAPT) and several tau kinases have been implicated in neurodegeneration, but only MAPT has a proven role in disease. We identified mutations in the gene encoding tau tubulin kinase 2 (TTBK2) as the cause of spinocerebellar ataxia type 11. Affected brain tissue showed substantial cerebellar degeneration and tau deposition. These data suggest that TTBK2 is important in the tau cascade and in spinocerebellar degeneration.

• Authors: Henry Houlden, Janel Johnson, Christopher Gardner-Thorpe, Tammaryn Lashley, Dena Hernandez, Paul Worth, Andrew B Singleton, David A Hilton, Janice Holton, Tamas Revesz, Mary B Davis, Paola Giunti, Paolo Giunti, Nicholas W Wood
• Journal: Nature genetics (Nat Genet) Vol. 39 Issue 12 Pg. 1434-6 (Dec 2007) ISSN: 1546-1718 [Electronic] United States
• PMID: 18037885 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Nonsense
• tau Proteins
• tau-tubulin kinase
• Protein Serine-Threonine Kinases

Topics

• Aged
• Aged, 80 and over
• Animals
• Brain (pathology)
• Codon, Nonsense
• Frameshift Mutation
• Humans
• Mice
• Phosphorylation
• Protein Serine-Threonine Kinases (genetics, metabolism)
• Rats
• Spinocerebellar Degenerations (genetics, pathology)
• tau Proteins (metabolism)