[Frontiers in Bioscience 16, 3252-3274, June 1, 2011]

The DFNB1 subtype of autosomal recessive non-syndromic hearing impairment

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

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. GJB2 gene and connexin-26
3.1. Gene and protein structures
3.2. Gene expression and protein localization
3.3. Function of connexin-26
4. Mutations in the coding region of GJB2
5. Mutations affecting non-coding parts of the gene or regulatory elements
5.1. Splice-site mutations
5.2. Promoter mutations
5.3. Large deletions
6. Genetic epidemiology of DFNB1 hearing impairment
7. Genotype-phenotype correlations
7.1. Age of onset and evolution of the hearing impairment
7.2. Severity of the hearing impairment
7.3. Modifier genes
7.4. Inner ear malformations
7.5. Temporal bone histopathology
7.6. Vestibular function
7.7. Audiologic phenotype of carriers
7.8. Outcome of cochlear implantation
8. Animal models
9. Acknowledgements
10. References

1. ABSTRACT

Inherited hearing impairment is a frequent and highly heterogeneous condition. Among the different subtypes of autosomal recessive non-syndromic hearing impairment, DFNB1 is remarkable for its high frequency in most populations. It is caused by mutations in the coding region or splice-sites of the GJB2 gene, or by mutations affecting regulatory sequences that are essential for the expression of this gene. GJB2 encodes connexin-26, a protein component of intercellular gap junctions, which play crucial physiological roles in the cochlea. Because of its high frequency, DFNB1 hearing impairment has received continued attention from researchers along the years, resulting in a wealth of data that is unparalleled among these disorders. Here we review our current knowledge on the genetic, molecular, and phenotypic aspects of this subtype of hearing impairment.