ERIC Number: EJ882336
Record Type: Journal
Publication Date: 2010-May
Abstractor: As Provided
A Mutation Affecting the Sodium/Proton Exchanger, "SLC9A6," Causes Mental Retardation with Tau Deposition
Garbern, James Y.; Neumann, Manuela; Trojanowski, John Q.; Lee, Virginia M.-Y.; Feldman, Gerald; Norris, Joy W.; Friez, Michael J.; Schwartz, Charles E.; Stevenson, Roger; Sima, Anders A. F.
Brain, v133 n5 p1391-1402 May 2010
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.
Descriptors: Severe Mental Retardation, Mental Retardation, Autism, Alzheimers Disease, Genetics, Family (Sociological Unit), Epilepsy, Multiple Disabilities, Brain, Diagnostic Tests, Biochemistry, Role, Cytology
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Publication Type: Journal Articles; Reports - Research
Education Level: N/A
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