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

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• dc.contributor.author Espino Guarch, Meritxell
• dc.contributor.author Fons-Llitjós, Mariona
• dc.contributor.author Murillo-Cuesta, Silvia
• dc.contributor.author Errasti-Murugarren, Ekaitz
• dc.contributor.author Celaya, Adelaida M.
• dc.contributor.author Girotto, Giorgia
• dc.contributor.author Vuckovic, Dragana
• dc.contributor.author Mezzavilla, Massimo
• dc.contributor.author Vilches, Clara
• dc.date.accessioned 2019-11-14T13:24:35Z
• dc.date.available 2019-11-14T13:24:35Z
• dc.date.issued 2018
• dc.description.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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Espino Guarch M, Font-Llitjós M, Murillo-Cuesta S, Errasti-Murugarren E, Celaya AM, Girotto G et al. Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss. eLife. 2018;7:e31511. DOI: 10.7554/eLife.31511
• dc.identifier.doi http://dx.doi.org/10.7554/eLife.31511
• dc.identifier.issn 2050-084X
• dc.identifier.uri http://hdl.handle.net/10230/42849
• dc.language.iso eng
• dc.publisher eLife
• dc.relation.ispartof eLife. 2018;7:e31511
• dc.rights © 2018, Espino Guarch et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword LAT2
• dc.subject.keyword Slc7a8
• dc.subject.keyword Age-related hearing loss
• dc.subject.keyword Auditory brainstem response
• dc.subject.keyword Chromosomes
• dc.subject.keyword Genes
• dc.subject.keyword Hearing loss
• dc.subject.keyword Human
• dc.subject.keyword Human biology
• dc.subject.keyword Knock-out mouse model
• dc.subject.keyword Medicine
• dc.subject.keyword Mouse
• dc.title Mutations in L-type amino acid transporter-2 support SLC7A8 as a novel gene involved in age-related hearing loss
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion