Espino Guarch Meritxell, Font-Llitjós Mariona, Murillo-Cuesta Silvia, Errasti-Murugarren Ekaitz, Celaya Adelaida M, Girotto Giorgia, Vuckovic Dragana, Mezzavilla Massimo, Vilches Clara, Bodoy Susanna, Sahún Ignasi, González Laura, Prat Esther, Zorzano Antonio, Dierssen Mara, Varela-Nieto Isabel, Gasparini Paolo, Palacín Manuel, Nunes Virginia
Experimental Genetics, Sidra Medical and Research Center, Doha, Qatar.
Genes, Disease and Therapy Program, Molecular Genetics Laboratory - IDIBELL, Barcelona, Spain.
Elife. 2018 Jan 22;7:e31511. doi: 10.7554/eLife.31511.
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 , 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.
年龄相关性听力损失（ARHL）是老年人中最常见的感觉缺陷。该疾病病因多因素，涉及的环境和遗传因素大多未知。SLC7A8/SLC3A2异二聚体是一种中性氨基酸交换体。在此，我们证明SLC7A8在小鼠内耳中表达，其缺失导致ARHL，这是由于不同耳蜗结构受损所致。这些发现使SLC7A8转运体成为人类ARHL的有力候选因素。因此，对一组ARHL患者和对照进行了筛查，发现了 中的几个变体，通过体外功能研究进一步研究了其作用。检测到患者变体（p.Val302Ile、p.Arg418His、p.Thr402Met和p.Val460Glu）的SLC7A8转运活性显著降低，进一步支持SLC7A8在ARHL中的致病作用。此外，我们的初步数据表明，相当一部分ARHL病例可能由SLC7A8突变解释。
