[Frontiers in Bioscience 17, 1251-1265, January 1, 2012]

Genetics of isolated auditory neuropathies

Francisco J. del Castillo1, 2, Ignacio del Castillo1, 2

1Unidad de Genetica Molecular, Hospital Universitario Ramon y Cajal, IRYCIS, Madrid, Spain, 2Centro de Investigacion Biomedica en Red de Enfermedades Raras, CIBERER, Madrid, Spain


1. Abstract
2. Introduction
3. OTOF gene and otoferlin
3.1. Gene and protein structures
3.2. Gene expression and protein localization
3.3. Function of otoferlin
3.4. Mutations of the OTOF gene in auditory neuropathy
4. DFNB59 gene and pejvakin
4.1. Gene and protein structures
4.2. Gene expression and protein localization
4.3. Function of pejvakin
4.4. Mutations of the DFNB59 gene in auditory neuropathy
5. DIAPH3 gene and diaphanous-3
5.1. Gene and protein structures
5.2. Gene expression and protein localization
5.3. Function of diaphanous-3
5.4. Mutations of the DIAPH3 gene in auditory neuropathy
6. Other genes reported to be involved in isolated auditory neuropathy
6.1. GJB2 (connexin-26) gene
6.2. Mitochondrial 12S rRNA gene
7. Future prospects
8. Acknowledgements
9. References


Auditory neuropathies are disorders combining absent or abnormal auditory brainstem responses with preserved otoacoustic emissions and/or cochlear microphonics. These features indicate a normal function of cochlear outer hair cells. Thus, the primary lesion might be located in the inner hair cells, in the auditory nerve or in the intervening synapse. Auditory neuropathy is observed in up to 10% of deaf infants and children, either as part of some systemic neurodegenerative diseases or as an isolated entity. Research on the genetic causes of isolated auditory neuropathies has been remarkably successful in the last few years. Here we review the current knowledge on the structure, expression and function of the genes and proteins so far known to be involved in these disorders, as well as the clinical features that are associated with mutations in the different genes. This knowledge is permitting to classify isolated auditory neuropathies into etiologically homogeneous types, so providing clues for the better diagnosis, management and therapy of the affected subjects.