TY  - JOUR
AU  - Preising, Markus N.
AU  - Görg, Boris
AU  - Friedburg, Christoph
AU  - Qvartskhava, Natalia
AU  - Budde, Birgit S.
AU  - Bonus, Michele
AU  - Toliat, Mohammad R.
AU  - Pfleger, Christopher
AU  - Altmüller, Janine
AU  - Herebian, Diran
AU  - Beyer, Mila
AU  - Zöllner, Helge J.
AU  - Wittsack, Hans-Jörg
AU  - Schaper, Jörg
AU  - Klee, Dirk
AU  - Zechner, Ulrich
AU  - Nürnberg, Peter
AU  - Schipper, Jörg
AU  - Schnitzler, Alfons
AU  - Gohlke, Holger
AU  - Lorenz, Birgit
AU  - Häussinger, Dieter
AU  - Bolz, Hanno J.
TI  - Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration
JO  - The FASEB journal
VL  - 33
IS  - 10
SN  - 1530-6860
CY  - Bethesda, Md.
PB  - FASEB
M1  - FZJ-2019-04062
SP  - 11507–11527
PY  - 2019
AB  - We previously reported that inactivation of the transmembrane taurine transporter (TauT or solute carrier 6a6) causes early retinal degeneration in mice. Compatible with taurine’s indispensability for cell volume homeostasis, protein stabilization, cytoprotection, antioxidation, and immuno- and neuromodulation, mice develop multisystemic dysfunctions (hearing loss; liver fibrosis; and behavioral, heart, and skeletal muscle abnormalities) later on. Here, by genetic, cell biologic, in vivo1H–magnetic resonance spectroscopy and molecular dynamics simulation studies, we conducted in-depth characterization of a novel disorder: human TAUT deficiency. Loss of TAUT function due to a homozygous missense mutation caused panretinal degeneration in 2 brothers. TAUTp.A78E still localized in the plasma membrane but is predicted to impact structural stabilization. 3H-taurine uptake by peripheral blood mononuclear cells was reduced by 95%, and taurine levels were severely reduced in plasma, skeletal muscle, and brain. Extraocular dysfunctions were not yet detected, but significantly increased urinary excretion of 8-oxo-7,8-dihydroguanosine indicated generally enhanced (yet clinically unapparent) oxidative stress and RNA oxidation, warranting continuous broad surveillance.—Preising, M. N., Görg, B., Friedburg, C., Qvartskhava, N., Budde, B. S., Bonus, M., Toliat, M. R., Pfleger, C., Altmüller, J., Herebian, D., Beyer, M., Zöllner, H. J., Wittsack, H.-J., Schaper, J., Klee, D., Zechner, U., Nürnberg, P., Schipper, J., Schnitzler, A., Gohlke, H., Lorenz, B., Häussinger, D., Bolz, H. J. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration.
LB  - PUB:(DE-HGF)16
C6  - pmid:31345061
UR  - <Go to ISI:>//WOS:000489166300075
DO  - DOI:10.1096/fj.201900914RR
UR  - https://juser.fz-juelich.de/record/864224
ER  -