Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11.
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.
Houlden
Henry
H
Department of Molecular Neuroscience, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. h.houlden@ion.ucl.ac.uk
Johnson
Janel
J
Gardner-Thorpe
Christopher
C
Lashley
Tammaryn
T
Hernandez
Dena
D
Worth
Paul
P
Singleton
Andrew B
AB
Hilton
David A
DA
Holton
Janice
J
Revesz
Tamas
T
Davis
Mary B
MB
Giunti
Paola
P
Giunti
Paolo
P
Wood
Nicholas W
NW
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000473:pathology; D018389:Codon, Nonsense; D016368:Frameshift Mutation; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
D018389:Codon, Nonsense; D016875:tau Proteins; C095903:tau-tubulin kinase; D017346:Protein Serine-Threonine Kinases