Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

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.

[img] PDF (Verlags-PDF) - Registered users only
1MB

Abstract

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
Language:English
Date:2010
Deposited On:03 Feb 2011 18:40
Last Modified:28 Nov 2013 01:23
Publisher:Oxford University Press
ISSN:0006-8950
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:10.1093/brain/awq071
PubMed ID:20395263
Citations:Web of Science®. Times Cited: 33
Google Scholar™
Scopus®. Citation Count: 32

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page