Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mildto-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/ NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (). The HI of 48 different genotypes was less severe P ! .0001 than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mildto-moderate HI (median 25-40 dB). Two genotypes-35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)-had significantly more-severe HI than that of 35delG homozygotes.

The dominant efferent innervation of the cochlea terminates on outer hair cells (OHCs), with acetylcholine (ACh) being its principal neurotransmitter. OHCs respond with a somatic shape change to alterations in their membrane potential, and this electromotile response is believed to provide mechanical feedback to the basilar membrane. We examine the effects of ACh on electromotile responses in isolated OHCs and attempt to deduce the mechanism of ACh action. Axial electromotile amplitude and cell compliance increase in the presence of the ligand. This response occurs with a significantly greater latency than membrane current and potential changes attributable to ACh and is contemporaneous with Ca 2ϩ release from intracellular stores. It is likely that increased axial compliance largely accounts for the increase in motility. The mechanical responses are probably related to a recently demonstrated slow efferent effect. The implications of the present findings related to commonly assumed efferent behavior in vivo are considered.

The inner ear is vulnerable against chronic suppurative otitis media. Older age increases this vulnerability. The proximity of the sensory cells to the potential source of harm (inflamed middle ear) may mean higher exposure, as reflected by the fact that sensory cells processing higher frequencies are more seriously damaged.

The etiologic role of measles virus in the pathogenesis of otosclerosis should be considered. The 14 negative samples may be genetically determined otosclerotic cases.