Busi Micol, Castiglione Alessandro
Department of Audiology, Orebro University Hospital, Interdisciplinary Research in Clinical Audiology-IRCA, Orebro University, 70116 Orebro, Sweden.
Audiol Res. 2024 Feb 26;14(2):254-263. doi: 10.3390/audiolres14020023.
Usher syndrome (US) is a clinically and genetically heterogeneous disorder that involves three main features: sensorineural hearing loss, retinitis pigmentosa (RP), and vestibular impairment. With a prevalence of 4-17/100,000, it is the most common cause of deaf-blindness worldwide. Genetic research has provided crucial insights into the complexity of US. Among nine confirmed causative genes, and are major players in US types 1 and 2, respectively, whereas is the sole confirmed gene associated with type 3. Variants in these genes also contribute to isolated forms of hearing loss and RP, indicating intersecting molecular pathways. While hearing loss can be adequately managed with hearing aids or cochlear implants (CIs), approved RP treatment modalities are lacking. Gene replacement and editing, antisense oligonucleotides, and small-molecule drugs hold promise for halting RP progression and restoring vision, enhancing patients' quality of life. Massively parallel sequencing has identified gene variants (e.g., in ) that influence CI results. Accordingly, preoperative genetic examination appears valuable for predicting CI success. To explore genetic mutations in CI recipients and establish correlations between implant outcomes and involved genes, we comprehensively reviewed the literature to gather data covering a broad spectrum of CI outcomes across all known US-causative genes. Implant outcomes were categorized as excellent or very good, good, poor or fair, and very poor. Our review of 95 cochlear-implant patients with US, along with their CI outcomes, revealed the importance of presurgical genetic testing to elucidate potential challenges and provide tailored counseling to improve auditory outcomes. The multifaceted nature of US demands a comprehensive understanding and innovative interventions. Genetic insights drive therapeutic advancements, offering potential remedies for the retinal component of US. The synergy between genetics and therapeutics holds promise for individuals with US and may enhance their sensory experiences through customized interventions.
尤塞氏综合征（US）是一种临床和遗传异质性疾病，具有三个主要特征：感音神经性听力损失、色素性视网膜炎（RP）和前庭功能障碍。其患病率为4-17/100,000，是全球范围内导致失聪失明的最常见原因。基因研究为US的复杂性提供了关键见解。在九个已确认的致病基因中， 和 分别是1型和2型US的主要致病基因，而 是与3型相关的唯一已确认基因。这些基因中的变异也导致了孤立形式的听力损失和RP，表明存在交叉的分子途径。虽然助听器或人工耳蜗（CI）可以有效管理听力损失，但目前缺乏批准的RP治疗方法。基因替代和编辑、反义寡核苷酸和小分子药物有望阻止RP进展并恢复视力，提高患者的生活质量。大规模平行测序已经确定了影响CI结果的基因变异（例如，在 中）。因此，术前基因检查对于预测CI成功率似乎很有价值。为了探索CI接受者的基因突变，并建立植入结果与相关基因之间的相关性，我们全面回顾了文献，以收集涵盖所有已知US致病基因的广泛CI结果的数据。植入结果分为优秀或非常好、良好、差或一般、非常差。我们对95例患有US的人工耳蜗植入患者及其CI结果的回顾表明，术前基因检测对于阐明潜在挑战并提供个性化咨询以改善听觉结果非常重要。US的多面性需要全面的理解和创新的干预措施。基因见解推动了治疗进展，为US的视网膜成分提供了潜在的治疗方法。遗传学与治疗学之间的协同作用为患有US的个体带来了希望，并可能通过定制干预措施增强他们的感官体验。
