Auditory neuropathy is a type of sensorineural hearing impairment in which the auditory brainstem response (ABR) is absent or severely distorted while otoacoustic emissions (OAEs), which are low level sounds originating in the cochlea due to the mechanical ... Auditory neuropathy is a type of sensorineural hearing impairment in which the auditory brainstem response (ABR) is absent or severely distorted while otoacoustic emissions (OAEs), which are low level sounds originating in the cochlea due to the mechanical activity of outer hair cells, are preserved. This suggests a primary lesion located in the inner hair cells, in the auditory nerve, or in the intervening synapse, but may also include damage to neuronal populations in the auditory pathway. Delmaghani et al. (2006) ascertained two 5-generation consanguineous families from isolated villages located in different regions of Iran with autosomal recessive, nonsyndromic, bilateral, prelingual sensorineural hearing impairment. In 1 family, affected individuals presented with profound deafness involving all frequencies that impeded speech acquisition. In the second family, pure-tone audiometry in affected individuals showed flat audiograms with hearing levels characteristic of severe hearing impairment. The findings of tests of ABR and synchronized spontaneous OAEs in the Iranian families met the diagnostic criteria for auditory neuropathy. Ebermann et al. (2007) reported a consanguineous Moroccan family in which 3 of 6 sibs had early childhood onset of slowly progressive hearing loss. Hearing aids in childhood were able to compensate for the hearing loss, but all patients had a strong decrease in speech intelligibility. Transient evoked OAEs and ABR tests were both abnormal, excluding auditory neuropathy. The findings suggested damage of the outer cochlear cells, although additional degeneration of auditory pathways at high levels could not be excluded. In addition, caloric provocation tests showed impaired central vestibular function. In this family, 5 of the sibs had combined severe cone-rod dystrophy associated with a homozygous mutation in the MERTK gene (604705.0003), which maps to chromosome 2q14. The 2 recessive disorders segregated independently, with only 2 sibs having both disorders. In 2 Turkish families with DFNB59, Collin et al. (2007) reported that transiently evoked OAEs were absent, indicating altered outer hair cell function.
The critical linkage interval for DFNB59 contained 12 known genes and as many ESTs. An exon-by-exon search for mutations in each of these genes revealed none in the known genes. In contrast, a homozygous C-to-T transition segregating with ... The critical linkage interval for DFNB59 contained 12 known genes and as many ESTs. An exon-by-exon search for mutations in each of these genes revealed none in the known genes. In contrast, a homozygous C-to-T transition segregating with the disease was discovered in a previously unknown gene, encoding pejvakin, and resulting in an R183W mutation (610219.0001). This mutation was found in 3 of the families; another missense mutation was found in the fourth family (610219.0002). The protein encoded by the DFNB59 gene was named pejvakin after the Persian word for echo. Although the DFNB59 locus is completely contained within the critical interval established for DFNB27 (605818), no mutations in pejvakin exons or splice junctions were detected in individuals with DFNB27, suggesting that causative genes in the 2 forms of hearing impairment are distinct. In 3 affected Moroccan sibs with hearing loss and central vestibular dysfunction, Ebermann et al. (2007) identified a homozygous mutation in the DFNB59 gene (610219.0003). Collin et al. (2007) identified a homozygous mutation in the DFNB59 gene (610219.0004) in 2 Turkish sibs with autosomal recessive nonsyndromic hearing loss. However, screening of 67 additional Turkish probands found the R183W mutation in 1 family, and screening of 83 Dutch patients failed to detect confirmatory mutations, suggesting that mutations in DFNB59 are not a common cause of hearing loss in these populations. In 2 unrelated consanguineous Iranian families with nonsyndromic deafness, Chaleshtori et al. (2007) identified 2 different mutations in the DFNB59 gene (610219.0005 and 610219.0006, respectively). Audiologic evaluation in 1 family showed absent ABR without OAEs, suggesting hearing loss of cochlear origin. In affected members of a large consanguineous Iranian pedigree segregating autosomal recessive progressive hearing loss, Schwander et al. (2007) identified homozygosity for a 1-bp deletion in the DFNB59 gene (610219.0007). Affected children showed moderate to profound deafness that was progressive in nature.