2. Academic Validation
  3. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration

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

  • FASEB J. 2019 Oct;33(10):11507-11527. doi: 10.1096/fj.201900914RR.
Markus N Preising 1,  Boris Görg 2,  Christoph Friedburg 1,  Natalia Qvartskhava 2,  Birgit S Budde 3,  Michele Bonus 4,  Mohammad R Toliat 3,  Christopher Pfleger 4,  Janine Altmüller 3 5,  Diran Herebian 6,  Mila Beyer 2,  Helge J Zöllner 7,  Hans-Jörg Wittsack 8,  Jörg Schaper 8,  Dirk Klee 8,  Ulrich Zechner 9 10,  Peter Nürnberg 3 5 11,  Jörg Schipper 12,  Alfons Schnitzler 7,  Holger Gohlke 4 13,  Birgit Lorenz 1,  Dieter Häussinger 2,  Hanno J Bolz 14 9
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Justus-Liebig University Giessen, Giessen, Germany.
  • 2 Department of Gastroenterology, Hepatology, and Infectious Diseases, University Hospital of Düsseldorf-Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 3 Cologne Center for Genomics, University of Cologne, Cologne, Germany.
  • 4 Institute for Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 5 Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
  • 6 Department of General Pediatrics, Neonatology, and Pediatric Cardiology, Medical Faculty, University Hospital Düsseldorf-Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 7 Institute of Clinical Neuroscience and Medical Psychology, University Hospital of Düsseldorf-Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 8 Department of Diagnostic and Interventional Radiology, University Hospital of Düsseldorf-Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 9 Senckenberg Centre for Human Genetics, Frankfurt on the Main, Germany.
  • 10 Institute of Human Genetics, Mainz University Medical Center, Mainz, Germany.
  • 11 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  • 12 Klinik für Hals-Nasen-Ohren Heilkunde, University Hospital of Düsseldorf-Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
  • 13 John von Neumann Institute for Computing (NIC)-Jülich Supercomputing Centre (JSC)-Structural Biochemistry, Institute of Complex Systems (ICS 6), Research Centre Jülich, Jülich, Germany.
  • 14 Institute of Human Genetics, University of Cologne, Cologne, Germany.
PMID: 31345061 DOI: 10.1096/fj.201900914RR
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 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.

Keywords

consanguinity; exome sequencing; homozygosity mapping.

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