Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-44243
Garbern, J Y; Neumann, M; Trojanowski, J Q; Lee, V M Y; Feldman, G; Norris, J W; Friez, M J; Schwartz, C E; Stevenson, R; Sima, A A F (2010). A mutation affecting the sodium/proton exchanger, SLC9A6, causes mental retardation with tau deposition. Brain: A Journal of Neurology, 133(Pt 5):1391-1402.
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We have studied a family with severe mental retardation characterized by the virtual absence of speech, autism spectrum disorder, epilepsy, late-onset ataxia, weakness and dystonia. Post-mortem examination of two males revealed widespread neuronal loss, with the most striking finding being neuronal and glial tau deposition in a pattern reminiscent of corticobasal degeneration. Electron microscopic examination of isolated tau filaments demonstrated paired helical filaments and ribbon-like structures. Biochemical studies of tau demonstrated a preponderance of 4R tau isoforms. The phenotype was linked to Xq26.3, and further analysis identified an in-frame 9 base pair deletion in the solute carrier family 9, isoform A6 (SLC9A6 gene), which encodes sodium/hydrogen exchanger-6 localized to endosomal vesicles. Sodium/hydrogen exchanger-6 is thought to participate in the targeting of intracellular vesicles and may be involved in recycling synaptic vesicles. The striking tau deposition in our subjects reveals a probable interaction between sodium/proton exchangers and cytoskeletal elements involved in vesicular transport, and raises the possibility that abnormalities of vesicular targeting may play an important role in more common disorders such as Alzheimer's disease and autism spectrum disorders.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology|
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||03 Feb 2011 19:40|
|Last Modified:||28 Nov 2013 02:23|
|Publisher:||Oxford University Press|
|Free access at:||Publisher DOI. An embargo period may apply.|
|Citations:||Web of Science®. Times Cited: 22|
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