Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration

Item Type:	Article
Title:	Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration
Creators Name:	Preising, M.N. and Görg, B. and Friedburg, C. and Qvartskhava, N. and Budde, B.S. and Bonus, M. and Toliat, M.R. and Pfleger, C. and Altmüller, J. and Herebian, D. and Beyer, M. and Zöllner, H.J. and Wittsack, H.J. and Schaper, J. and Klee, D. and Zechner, U. and Nürnberg, P. and Schipper, J. and Schnitzler, A. and Gohlke, H. and Lorenz, B. and Häussinger, D. and Bolz, H.J.
Abstract:	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 vivo (1)H-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. TAUT(p.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.
Keywords:	Exome Sequencing, Homozygosity Mapping, Consanguinity
Source:	FASEB Journal
ISSN:	0892-6638
Publisher:	Federation of American Societies for Experimental Biology
Volume:	33
Number:	10
Page Range:	11507-11527
Date:	October 2019
Official Publication:	https://doi.org/10.1096/fj.201900914RR
PubMed:	View item in PubMed

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