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Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss

journal contribution
submitted on 2024-07-15, 07:15 and posted on 2024-07-15, 07:15 authored by 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

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 inSLC7A8, 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.

Other Information

Published in: eLife
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.7554/elife.31511

Funding

Qatar National Research Fund (JSREP07-013-3-006), Age-related hearing loss in Qatar: a genomic approach to identify causative genes.

CIBERER (ACCI 2016).

CIBERER (ACCI 2017).

Generalitat de Catalunya (SGR 2014/1125).

Ministerio de Ciencia e Innovación (SAF2016-79956-R).

Seventh Framework Programme (TARGEAR FP7-PEOPLE-2013-IAPP).

Ministerio de Ciencia e Innovación (SAF2014-53979-R-FEDER).

Ministerio de Ciencia e Innovación (SAF2015-64869-R-FEDER).

Generalitat de Catalunya (SGR2009-1355).

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

Generalitat de Catalunya (SGR2009-1490).

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

History

Language

  • English

Publisher

eLife Sciences Publications

Publication Year

  • 2018

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Sidra Medicine
  • Sidra Medical and Research Center (2015-2017)

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