Genomics and hearing impairment

Hearing impairment is clinically and genetically heterogeneous. There are > 400 disorders in which hearing impairment is a characteristic of the syndro me, and family studies demonstrate that there are at least 30 autosomal loc i for nonsyndromic hearing impairment. The genes that have been identified encode diaphanous (HDIAI), alpha-tectorin (TECTA) the transcription factor POU4F3, connexin 26 (GJB2), and two unconventional myosins (MYO7A and MYO15 ), and four novel proteins (PDS, COCH, DFNA5, DFNB9). The same clinical phe notype in hearing-impaired individuals, even those within the same Family, can result from mutations in different genes. Conversely, mutations in the same gene can result in a variety of clinical phenotypes with different mod es of inheritance. For example, mutations in the gene encoding MYO7A cause Usher syndrome type IB, autosomal-recessive nonsyndromic hearing impairment (DFNB2), and autosomal-dominant nonsyndromic hearing impairment [DFNA11]. Additionally, the mouse ortholog of the MYO7A gene is the shaker-1 gene. Mo use models such as shaker-1 have facilitated the identification of genes th at cause hearing impairment in humans. The availability of high-resolution maps of the human and mouse genomes and new technologies for gene identific ation are advancing molecular understanding of hearing impairment and the c omplex mechanisms of the auditory system.