title: Genetics of vestibular disorders: pathophysiological insights.
abstract: The two most common vestibular disorders are motion sickness and vestibular migraine, affecting 30 and 1-2% of the population respectively. Both are related to migraine and show a familial trend. Bilateral vestibular hypofunction is a rare condition, and some of patients also present cerebellar ataxia and neuropathy. We present recent advances in the genetics of vestibular disorders with familial aggregation. The clinical heterogeneity observed in different relatives of the same families suggests a variable penetrance and the interaction of several genes in each family. Some Mendelian sensorineural hearing loss also exhibits vestibular dysfunction, including DFNA9, DFNA11, DFNA15 and DFNA28. However, the most relevant finding during the past years is the familial clustering observed in Meniere's disease. By using whole exome sequencing and combining bioinformatics tools, novel variants in DTNA and FAM136A genes have been identified in familial Meniere's disease, and this genomic strategy will facilitate the discovery of the genetic basis of familial vestibular disorders.
authors.affiliation: Otology and Neurotology Group CTS495, Department of Genomic Medicine, GENYO - Centre for Genomics and Oncological Research - Pfizer/University of Granada/Junta de Andalucía, PTS, 18016, Granada, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Frejo
authors.affiliation: German Center for Vertigo and Balance Disorders, Munich, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.affiliation: Department of Otolaryngology, San Raffaelle Scientific Institute, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Teggi
authors.affiliation: Otology and Neurotology Group CTS495, Department of Genomic Medicine, GENYO - Centre for Genomics and Oncological Research - Pfizer/University of Granada/Junta de Andalucía, PTS, 18016, Granada, Spain. antonio.lopezescamez@genyo.es.|Department of Otolaryngology, Granada University Hospital, 18012, Granada, Spain. antonio.lopezescamez@genyo.es.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Lopez-Escamez
authors.affiliation: German Center for Vertigo and Balance Disorders, Munich, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
mesh_terms: D019295:Computational Biology; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics; D000081412:Myosin VIIa; D009218:Myosins; D050821:Transcription Factor Brn-3C / Q000235:genetics; D014157:Transcription Factors; D015837:Vestibular Diseases / Q000145:classification / Q000235:genetics* / Q000503:physiopathology*
chemical_list: C110668:COCH protein, human; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; C000601377:FAM136A protein, human; C470830:GRHL2 protein, human; D018398:Homeodomain Proteins; C000631455:MYO7A protein, human; D024101:Mitochondrial Proteins; D000081412:Myosin VIIa; C111223:POU4F3 protein, human; D050821:Transcription Factor Brn-3C; D014157:Transcription Factors; D009218:Myosins
keywords: Meniere disease; Motion sickness; Vestibular disorders; Vestibular migraine; Whole exome sequencing