1. Chromosomes and Gene Expression
  2. Human Biology and Medicine
Download icon

Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in Age-Related Hearing Loss

  1. Meritxell Espino Gaurch  Is a corresponding author
  2. Mariona Font-Llitjós
  3. Silvia Murillo-Cuesta
  4. Ekaitz Errasti- Murugarren
  5. Adelaida M Celaya
  6. Giorgia Girotto
  7. Dragana Vuckovic
  8. Massimo Mezzavilla
  9. Clara Vilches
  10. Susanna Bodoy
  11. Ignasi Sahún
  12. Laura González
  13. Esther Prat
  14. Antonio Zorzano
  15. Mara Dierssen
  16. Isabel Varela-Nieto
  17. Paolo Gasparini
  18. Manuel Palacín  Is a corresponding author
  19. Virginia Nunes  Is a corresponding author
  1. Sidra Medical and Research Center, Qatar
  2. Institut d'Investigació Biomédica de Bellvitge (IDIBELL), Spain
  3. Biomedical Research Networking Centre on Rare Diseases (CIBERER), Spain
  4. Institute for Research in Biomedicine (IRB Barcelona), Spain
  5. University of Trieste, Italy
Research Article
  • Cited 1
  • Views 1,291
  • Annotations
Cite as: eLife 2018;7:e31511 doi: 10.7554/eLife.31511

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.

Article and author information

Author details

  1. Meritxell Espino Gaurch

    Experimental Genetics, Sidra Medical and Research Center, Doha, Qatar
    For correspondence
    mespinoguarch@sidra.org
    Competing interests
    The authors declare that no competing interests exist.
  2. Mariona Font-Llitjós

    Molecular Genetics Laboratory, Institut d'Investigació Biomédica de Bellvitge (IDIBELL), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Silvia Murillo-Cuesta

    Biomedical Research Networking Centre on Rare Diseases (CIBERER), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Ekaitz Errasti- Murugarren

    Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Adelaida M Celaya

    Biomedical Research Networking Centre on Rare Diseases (CIBERER), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Giorgia Girotto

    Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy
    Competing interests
    The authors declare that no competing interests exist.
  7. Dragana Vuckovic

    Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy
    Competing interests
    The authors declare that no competing interests exist.
  8. Massimo Mezzavilla

    Experimental Genetics, Sidra Medical and Research Center, Doha, Qatar
    Competing interests
    The authors declare that no competing interests exist.
  9. Clara Vilches

    Molecular Genetics Laboratory, Institut d'Investigació Biomédica de Bellvitge (IDIBELL), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Susanna Bodoy

    Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  11. Ignasi Sahún

    Biomedical Research Networking Centre on Rare Diseases (CIBERER), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  12. Laura González

    Molecular Genetics Laboratory, Institut d'Investigació Biomédica de Bellvitge (IDIBELL), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  13. Esther Prat

    Molecular Genetics Laboratory, Institut d'Investigació Biomédica de Bellvitge (IDIBELL), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  14. Antonio Zorzano

    Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  15. Mara Dierssen

    Biomedical Research Networking Centre on Rare Diseases (CIBERER), Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-0853-6865
  16. Isabel Varela-Nieto

    Biomedical Research Networking Centre on Rare Diseases (CIBERER), Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  17. Paolo Gasparini

    Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy
    Competing interests
    The authors declare that no competing interests exist.
  18. Manuel Palacín

    Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
    For correspondence
    manuel.palacin@irbbarcelona.org
    Competing interests
    The authors declare that no competing interests exist.
  19. Virginia Nunes

    Molecular Genetics Laboratory, Institut d'Investigació Biomédica de Bellvitge (IDIBELL), Barcelona, Spain
    For correspondence
    vnunes@idibell.cat
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-5747-9310

Funding

Spanish Health Institute Carlos III- FIS (PI13/00121-R-FEDER)

  • Virginia Nunes

Spanish Ministry of Science and Innovation (SAF2014-53979-R-FEDER)

  • Isabel Varela-Nieto

Spanish Health Institute Carlos III-FIS (PI16/00267-R-Feder)

  • Virginia Nunes

CIBERER (ACCI 2017)

  • Isabel Varela-Nieto
  • Manuel Palacín
  • Virginia Nunes

Spanish Ministry of Science and Innovation (SAF2015-64869-R-FEDER)

  • Manuel Palacín

Generalitat de Catalunya (SGR2009-1490)

  • Virginia Nunes

Qatar National Research Fund (JSREP07-013-3-006)

  • Meritxell Espino Gaurch

CIBERER (ACCI 2016)

  • Isabel Varela-Nieto
  • Manuel Palacín
  • Virginia Nunes

TARGEAR (FP7-PEOPLE-2013-IAPP)

  • Isabel Varela-Nieto

Generalitat de Catalunya (SGR2009-1355)

  • Manuel Palacín

Generalitat de Catalunya (SGR 2014/1125)

  • Mara Dierssen

Spanish Ministry of Science and Innovation (SAF2016-79956-R)

  • Mara Dierssen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal experimentation complied with the ARRIVE guidelines and was conducted in accordance with Spanish (RD 53/2013) and European (Directive 2010/63/EU) legislations. All protocols used in this study were reviewed and approved by the Institutional Animal Care and Use Committee at IDIBELL in a facility accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAELAC accredited facility, B900010). Mice procedures were done according with scientific, humane, and ethical principles. The studied mouse model did not show phenotype differences comparing male and female. Thus, to ensure that our research represents both genders, the studies describes in this work were performed using both sexes equitably. The number of biological and experimental replicates is detailed in the legend of each figure.

Human subjects: Ethical Consent Published in:Esko T, Mezzavilla M, Nelis M, Borel C, Debniak T, Jakkula E, et al. Genetic characterization of northeastern Italian population isolates in the context of broader European genetic diversity. Eur J Hum Genet. 2013;21(6):659-65.

Reviewing Editor

  1. Jeremy Nathans, Reviewing Editor, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: August 24, 2017
  2. Accepted: January 18, 2018
  3. Accepted Manuscript published: January 22, 2018 (version 1)
  4. Version of Record published: February 13, 2018 (version 2)
  5. Version of Record updated: March 5, 2018 (version 3)
  6. Version of Record updated: March 13, 2018 (version 4)

Copyright

© 2018, Espino Gaurch et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,291
    Page views
  • 266
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Zaijun Ma et al.
    Research Article Updated
    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology
    Bryan J Matthews, David J Waxman
    Research Article Updated