A Mutation Affecting the Sodium/Proton Exchanger, "SLC9A6," Causes Mental Retardation with Tau Deposition

Autor/inn/en	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.
Titel	A Mutation Affecting the Sodium/Proton Exchanger, "SLC9A6," Causes Mental Retardation with Tau Deposition
Quelle	In: Brain, 133 (2010) 5, S.1391-1402 (12 Seiten) PDF als Volltext Verfügbarkeit
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	0006-8950
DOI	10.1093/brain/awq071
Schlagwörter	Severe Mental Retardation; Autism; Alzheimers Disease; Genetics; Family (Sociological Unit); Epilepsy; Multiple Disabilities; Brain; Diagnostic Tests; Biochemistry; Role; Cytology + Suchen Sie Ihr Suchwort? Autismus; Humangenetik; Familie; Epilepsie; Multiple disability; Mehrfachbehinderung; Gehirn; Diagnostic test; Diagnostischer Test; Biochemie; Rollen; Zytologie
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. (As Provided).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2017/4/10