Vestibular symptoms and associated gene mutations in non-syndromic hereditary deafness: A review of the literature and the database

The recent advent of next-generation sequencing has led to the identification of novel gene mutations that cause non-syndromic deafness, characterized by sensorineural hearing loss with or without vertigo as the sole symptom. As the molecular function and tissue expression of these deafness genes are unique to the cochleovestibular system, studies on the vestibular symptoms associated with these deafness gene mutations have led to a better understanding of the molecular mechanisms underlying the manifestation of peripheral vertigo/dizziness. We have compiled a comprehensive list of deafness genes associated with vestibular symptoms and non-syndromic deafness by reviewing the information deposited in the English literature and in the Deafness Gene Database (Hereditary Hearing Loss Homepage, the University of Iowa). Mutations of 23 deafness genes (KCNQ 4, LMX 1 A, COCH, MYO 7 A, COL 11 A 2, MYH 9, KITLG, SLC 12 A 2, SLC 26 A 4, STRC, OTOG, USH 1 C, PCDH 15, GRXCR 1, ESPIN, MYO 6, PJVK, PTPRQ, OTOGL, CLIC 5, ROR 1, ESRP 1, POU 3 F 4) are reported to be associated with clinical vestibular symptoms, radiologic vestibular anomalies, and/or abnormal results of vestibular function tests, such as the caloric test and rotatory chair test. Genes such as LMX 1 A, KITLG, SLC 12 A 2, OTOGL, ROR 1, and ESRP 1 were identified as being associated with nonsyndromic deafness and vestibular symptoms by means of whole-exome sequencing after 2010, when the molecular diagnosis of deafness by next-generation sequencing was first reported in the English literature. Tissue expressions of MYO 7 A, MYH 9, STRC, USH 1 C, PCDH 15, GRXCR 1, ESPIN, MYO 6, and CLIC 5 have been found in the hair cells and have been recognized as playing roles in hair cell structures, such as the stereocilia. COL 11 A 2, OTOG and OTOGL encode extracellular proteins of the otolithic membrane and tectorial membrane. COCH protein is the most inner ear-abundant protein specific to the perilymph fluid. These non -syndromic deafness genes play important roles in vestibular functions.