eLife (Jan 2018)
Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss
- Meritxell Espino Guarch,
- Mariona Font-Llitjós,
- Silvia Murillo-Cuesta,
- Ekaitz Errasti- Murugarren,
- Adelaida M Celaya,
- Giorgia Girotto,
- Dragana Vuckovic,
- Massimo Mezzavilla,
- Clara Vilches,
- Susanna Bodoy,
- Ignasi Sahún,
- Laura González,
- Esther Prat,
- Antonio Zorzano,
- Mara Dierssen,
- Isabel Varela-Nieto,
- Paolo Gasparini,
- Manuel Palacín,
- Virginia Nunes
Affiliations
- Meritxell Espino Guarch
- ORCiD
- Experimental Genetics, Sidra Medical and Research Center, Doha, Qatar; Genes, Disease and Therapy Program, Molecular Genetics Laboratory - IDIBELL, Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
- Mariona Font-Llitjós
- Genes, Disease and Therapy Program, Molecular Genetics Laboratory - IDIBELL, Barcelona, Spain; Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain
- Silvia Murillo-Cuesta
- ORCiD
- Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain; Alberto Sols Biomedical Research Institute (CSIC/UAM), Madrid, Spain; Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
- Ekaitz Errasti- Murugarren
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain
- Adelaida M Celaya
- Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain; Alberto Sols Biomedical Research Institute (CSIC/UAM), Madrid, Spain
- Giorgia Girotto
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Medical Genetics, Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, Italy
- Dragana Vuckovic
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Medical Genetics, Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, Italy
- Massimo Mezzavilla
- Experimental Genetics, Sidra Medical and Research Center, Doha, Qatar
- Clara Vilches
- Genes, Disease and Therapy Program, Molecular Genetics Laboratory - IDIBELL, Barcelona, Spain
- Susanna Bodoy
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain
- Ignasi Sahún
- Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain; Center for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
- Laura González
- Genes, Disease and Therapy Program, Molecular Genetics Laboratory - IDIBELL, Barcelona, Spain; Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain
- Esther Prat
- Genes, Disease and Therapy Program, Molecular Genetics Laboratory - IDIBELL, Barcelona, Spain; Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain; Genetics Section, Physiological Sciences Department, Health Sciences and Medicine Faculty, University of Barcelona, Barcelona, Spain
- Antonio Zorzano
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Biochemistry and Molecular Biomedicine Department, Faculty of Biology, University of Barcelona, Barcelona, Spain; Biomedical Research Networking Centre on Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain
- Mara Dierssen
- ORCiD
- Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain; Center for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain
- Isabel Varela-Nieto
- Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain; Alberto Sols Biomedical Research Institute (CSIC/UAM), Madrid, Spain; Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
- Paolo Gasparini
- Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Medical Genetics, Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, Italy
- Manuel Palacín
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain; Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain; Biochemistry and Molecular Biomedicine Department, Faculty of Biology, University of Barcelona, Barcelona, Spain
- Virginia Nunes
- ORCiD
- Genes, Disease and Therapy Program, Molecular Genetics Laboratory - IDIBELL, Barcelona, Spain; Biomedical Research Networking Centre on Rare Diseases (CIBERER), Institute of Health Carlos III, Barcelona, Spain; Genetics Section, Physiological Sciences Department, Health Sciences and Medicine Faculty, University of Barcelona, Barcelona, Spain
- DOI
- https://doi.org/10.7554/eLife.31511
- Journal volume & issue
-
Vol. 7
Abstract
Age-related hearing loss (ARHL) is the most common sensory deficit in the elderly. The disease has a multifactorial etiology with both environmental and genetic factors involved being largely unknown. SLC7A8/SLC3A2 heterodimer is a neutral amino acid exchanger. Here, we demonstrated that SLC7A8 is expressed in the mouse inner ear and that its ablation resulted in ARHL, due to the damage of different cochlear structures. These findings make SLC7A8 transporter a strong candidate for ARHL in humans. Thus, a screening of a cohort of ARHL patients and controls was carried out revealing several variants in SLC7A8, whose role was further investigated by in vitro functional studies. Significant decreases in SLC7A8 transport activity was detected for patient’s variants (p.Val302Ile, p.Arg418His, p.Thr402Met and p.Val460Glu) further supporting a causative role for SLC7A8 in ARHL. Moreover, our preliminary data suggest that a relevant proportion of ARHL cases could be explained by SLC7A8 mutations.
Keywords
