Mei Christine, Dong Hongsong, Nisenbaum Eric, Thielhelm Torin, Nourbakhsh Aida, Yan Denise, Smeal Molly, Lundberg Yesha, Hoffer Michael E, Angeli Simon, Telischi Fred, Nie Guohui, Blanton Susan H, Liu Xuezhong
Department of Otolaryngology, University of Miami, Coral Gables, FL, United States.
Shenzhen Second People's Hospital, Shenzhen, China.
Front Neurol. 2021 Feb 5;12:633207. doi: 10.3389/fneur.2021.633207. eCollection 2021.
Vestibular disorders (VDs) are a clinically divergent group of conditions that stem from pathology at the level of the inner ear, vestibulocochlear nerve, or central vestibular pathway. No etiology can be identified in the majority of patients with VDs. Relatively few families have been reported with VD, and so far, no causative genes have been identified despite the fact that more than 100 genes have been identified for inherited hearing loss. Inherited VDs, similar to deafness, are genetically heterogeneous and follow Mendelian inheritance patterns with all modes of transmission, as well as multifactorial inheritance. With advances in genetic sequencing, evidence of familial clustering in VD has begun to highlight the genetic causes of these disorders, potentially opening up new avenues of treatment, particularly in Meniere's disease and disorders with comorbid hearing loss, such as Usher syndrome. In this review, we aim to present recent findings on the genetics of VDs, review the role of genetic sequencing tools, and explore the potential for individualized medicine in the treatment of these disorders. A search of the PubMed database was performed for English language studies relevant to the genetic basis of and therapies for vestibular disorders, using search terms including but not limited to: "genetics," "genomics," "vestibular disorders," "hearing loss with vestibular dysfunction," "individualized medicine," "genome-wide association studies," "precision medicine," and "Meniere's syndrome." Increasing numbers of studies on vestibular disorder genetics have been published in recent years. Next-generation sequencing and new genetic tools are being utilized to unearth the significance of the genomic findings in terms of understanding disease etiology and clinical utility, with growing research interest being shown for individualized gene therapy for some disorders. The genetic knowledge base for vestibular disorders is still in its infancy. Identifying the genetic causes of balance problems is imperative in our understanding of the biology of normal function of the vestibule and the disease etiology and process. There is an increasing effort to use new and efficient genetic sequencing tools to discover the genetic causes for these diseases, leading to the hope for precise and personalized treatment for these patients.
前庭疾病（VDs）是一组临床症状各异的病症，其病因源于内耳、前庭蜗神经或中枢前庭通路的病变。大多数VDs患者无法明确病因。报道的VDs相关家族相对较少，尽管已鉴定出100多个遗传性听力损失相关基因，但迄今为止尚未发现致病基因。与耳聋相似，遗传性VDs具有遗传异质性，遵循所有遗传方式的孟德尔遗传模式以及多基因遗传。随着基因测序技术的进步，VDs家族聚集性的证据已开始凸显这些疾病的遗传病因，这可能为治疗开辟新途径，尤其是在梅尼埃病和伴有听力损失的疾病（如Usher综合征）中。在本综述中，我们旨在介绍VDs遗传学的最新研究结果，回顾基因测序工具的作用，并探讨个性化医疗在这些疾病治疗中的潜力。我们使用包括但不限于“遗传学”“基因组学”“前庭疾病”“伴有前庭功能障碍的听力损失”“个性化医疗”“全基因组关联研究”“精准医学”和“梅尼埃综合征”等检索词，在PubMed数据库中搜索了与前庭疾病的遗传基础和治疗相关的英文研究。近年来，关于前庭疾病遗传学的研究数量不断增加。下一代测序和新的基因工具正被用于挖掘基因组研究结果在理解疾病病因和临床应用方面的意义，对某些疾病的个性化基因治疗的研究兴趣也在不断增加。前庭疾病的遗传知识库仍处于起步阶段。确定平衡问题的遗传原因对于我们理解前庭正常功能的生物学机制以及疾病病因和进程至关重要。人们越来越努力使用新的高效基因测序工具来发现这些疾病的遗传原因，从而为这些患者带来精准和个性化治疗的希望。
