[Non-syndromic hereditary hearing impairment]

Hearing impairment is the most common sensorineural disorder in humans. Approximately one of thousand new-borns is affected by severe to profound deafness at birth or during early childhood. Genetic causes account for around half of these cases of prelingual hearing impairment and the remainder are attributed to environmental factors. Genetic causes of hearing impairment in combination with a syndrome as Usher, Pendred are distinguished from non-syndromic hearing impairment. In the last years a tremendous growth in the localisation and identification of genes for non-syndromic hereditary hearing impairment has evolved. It has become clear that these conditions are genetically extremely heterogeneous. Approximately 120 different gene loci associated with non syndromic hearing impairment have been identified. Presently 54 gene loci associated with autosomal dominant mode of inheritance and 67 gene loci with autosomal recessive mode of inheritance have been identified; 7 are X-chromosome linked and 4 mitochondrial. Of these, 19 genes have been characterised for autosomal dominant (DFNA), 20 for autosomal recessive (DFNB), and 2 for X-linked (DFN) disorders. These genes encode proteins of diverse functions, including transcription factors, cytoskeletal and extracellular matrix components, and ion channels. Despite this heterogeneity, up to 50 % of prelingual recessive non-syndromic deafness can be attributed to mutations in the GJB2 gene (Connexin-26, gap-junction protein). However, the diversity of genes and genetic loci implicated in hearing loss illustrates the complexity of the genetic basis of hearing. Knowing the gene and the function of its products helps understanding the mechanisms of hearing.