Recent advances in next generation sequencing techniques (NGS) are increasing the number of novel genes associated with cerebellar and vestibular disorders. We have summarized clinical and molecular genetics findings in neuro-otolology during the last 2 years.
Whole-exome and targeted sequencing have defined the genetic basis of dizziness including new genes causing ataxia: GBA2, TGM6, ANO10 and SYT14. Novel mutations in KCNA1 and CACNA1A genes are associated with episodic ataxia type 1 and type 2, respectively. Moreover, new variants in genes such as COCH, MYO7A and POU4F3 are associated with nonsyndromic deafness and vestibular dysfunction. Several susceptibility loci have been linked to familial vestibular migraine, suggesting genetic heterogeneity, but no specific gene has been identified. Finally, loci for complex and heterogeneous diseases such as bilateral vestibular hypofunction or familial Ménière disease have not been identified yet, despite their strong familial aggregation.
Cerebellar and vestibular disorders leading to dizziness or episodic vertigo may show overlapping clinical features. A deep phenotyping including a complete familial history is a key step in performing a reliable molecular genetic diagnosis using NGS. Personalized molecular medicine will be essential to understand disease mechanisms as well as to improve their diagnosis and treatment.
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aOtology and Neurotology Group CTS495, Human DNA Variability Department, GENYO. Centre for Genomics and Oncological Research (GENyO), Pfizer/University of Granada/Andalusian Regional Government, PTS Granada
bDepartment of Otolaryngology, Hospital San Agustin, Linares, Jaen
cDepartment of Otolaryngology, Hospital de Poniente, El Ejido, Almería, Spain
Correspondence to Dr Jose A. Lopez-Escamez, Otology and Neurotology Group CTS495, GENYO. Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, Avenida de la Ilustración, 114, 18016 Granada, Spain. Tel: +34 958 715 500 160; e-mail: email@example.com
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