Sensorineural hearing loss (SNHL) is the most prevalent genetic sensory defect in humans. It is estimated that globally 1:1000 children born have profound hearing loss. Non-syndromic SNHL accounts for approximately 70% of hereditary hearing loss. In addition, 80% of the non-syndromic SNHL cases have an autosomal recessive mode of inheritance (ARNSHL), also known as DFNB. To date, few dozens of genes and gene loci have been implicated in DFNB.
DFNB59 has been described in families in which affected individuals presented with either auditory neuropathy or hearing loss of cochlear origin. 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.
Ebermann et al. (2007) identified a consanguineous family from Morocco segregating autosomal recessive congenital progressive hearing loss (ARNSHL) and retinal degeneration. Detailed clinical investigation of the six siblings revealed combined severe cone-rod dystrophy (CORD) and severe/profound hearing impairment in two of them, while there is isolated CORD in three and non-syndromic profound hearing loss in one. The disease loci were mapped to chromosome 2q31.1-2q32.1 for ARNSHL and to 2q13-2q14.1 for CORD, respectively. The retinal phenotype was shown to be due to homozygosity for a novel splice site mutation, c.2189+1G>T, in the retinitis pigmentosa gene MERTK. Mutation screening in the DFNB59 gene revealed homozygosity for a 1-bp insertion in exon 2 (c.113_114insT), predicting a truncated protein of 47 amino acids, in all three hearing impaired subjects. Detailed audiological investigation indicated hair cell dysfunction and, in contrast to cases reported previously, excluded auditory neuropathy. Moreover, all patients in the family with homozygosity for the DFNB59 mutation displayed central vestibular dysfunction.
Shahin et al. (2010) reported a consanguineous Palestinian family in which four members (one male and three females) had prelingual bilateral autosomal recessive non-syndromic hearing loss (NSHL). Shahin et al. (2010) identified a nonsense mutation (c.762C>T; Arg136STOP) in the PJVK gene in this family. No otoacoustic emission (OAE) distortion products were present in deaf relatives of this family, indicating that auditory neuropathy is highly unlikely to be present.
Borck et al. (2011) reported three consanguineous families of Arab origin with prelingual non-syndromic hearing impairment and absent otoacoustic emissions in a total of eight affected individuals. All families originated from the same village and bear the same family name. At the molecular level, Borck et al. (2011) identified a c.406C>T (p.R136X) nonsense mutation in the DFNB59 gene in affected individuals from these families.