Novel Pathogenic Variants in PJVK, the Gene Encoding Pejvakin, in Subjects with Autosomal Recessive Non-Syndromic Hearing Impairment and Auditory Neuropathy Spectrum Disorder

Pathogenic variants in the PJVK gene cause the DFNB59 type of autosomal recessive non-syndromic hearing impairment (AR-NSHI). Phenotypes are not homogeneous, as a few subjects show auditory neuropathy spectrum disorder (ANSD), while others show cochlear hearing loss. The numbers of reported cases and pathogenic variants are still small to establish accurate genotype-phenotype correlations. We investigated a cohort of 77 Spanish familial cases of AR-NSHI, in whom DFNB1 had been excluded, and a cohort of 84 simplex cases with isolated ANSD in whom OTOF variants had been excluded. All seven exons and exon-intron boundaries of the PJVK gene were sequenced. We report three novel DFNB59 cases, one from the AR-NSHI cohort and two from the ANSD cohort, with stable, severe to profound NSHI. Two of the subjects received unilateral cochlear implantation, with apparent good outcomes. Our study expands the spectrum of PJVK mutations, as we report four novel pathogenic variants: p.Leu224Arg, p.His294Ilefs*43, p.His294Asp and p.Phe317Serfs*20. We review the reported cases of DFNB59, summarize the clinical features of this rare subtype of AR-NSHI and discuss the involvement of PJVK in ANSD.

Electrocochleography in Auditory Neuropathy Related to Mutations in the OTOF or OPA1 Gene

Auditory Neuropathy (AN) is a hearing disorder characterized by disruption of temporal coding of acoustic signals in auditory nerve fibers resulting in the impairment of auditory perceptions that rely on temporal cues. Mutations in several nuclear and mitochondrial genes have been associated to the most well-known forms of AN. Underlying mechanisms include both pre-synaptic and post-synaptic disorders affecting inner hair cell (IHC) depolarization, neurotransmitter release from ribbon synapses, spike initiation in auditory nerve terminals, loss of nerve fibers and impaired conduction, all occurring in the presence of normal physiological measures of outer hair cell (OHC) activities (otoacoustic emissions [OAEs] and cochlear microphonic [CM]). Disordered synchrony of auditory nerve activity has been suggested as the basis of both the profound alterations of auditory brainstem responses (ABRs) and impairment of speech perception. We will review how electrocochleography (ECochG) recordings provide detailed information to help objectively define the sites of auditory neural dysfunction and their effect on inner hair cell receptor summating potential (SP) and compound action potential (CAP), the latter reflecting disorders of ribbon synapses and auditory nerve fibers.

A Rare Case of Perrault Syndrome with Auditory Neuropathy Spectrum Disorder: Cochlear Implantation Treatment and Literature Review

Perrault syndrome (PRLTS) is a rare autosomal recessive disorder characterised by ovarian failure in females and sensorineural hearing loss (SNHL) in both genders. In the present paper we describe a child affected by PRLTS3, due to CLPP homozygous mutations, presenting auditory neuropathy spectrum disorder (ANSD) with bilateral progressive SNHL. This is the first case reported in the literature of an ANSD in PRLTS3. CLPP is a nuclear encoded mitochondrial protease directed at the mitochondrial matrix. It is encoded on chromosome 19. This protease participates in mitochondrial protein quality control by degrading misfolded or damaged proteins, thus maintaining the normal metabolic function of the cell. In PRLTS3, the peptidase activity of CLPP is suppressed. Neurological impairments involved in PRLTS3 suggest that the pathogenic mutations in CLPP might trigger a mitochondrial dysfunction. A comprehensive description of the clinical and audiological presentation, as well as the issues related to cochlear implant (CI) procedure and the results, are addressed and discussed. A brief review of the literature on this topic is also provided.

Oto acoustic emissions in early detection of sensorineural hearing loss in high-risk neonates

<p><strong>Background: </strong>Early identification of congenital hearing loss and early intervention ameliorated many adverse consequences. This study was performed to observe effectiveness of otoacoustic emission in screening of hearing loss in high-risk babies.</p><p><strong>Methods: </strong>Prospective study on 45 high-risk newborns delivered during period of 2013-2014. Selective newborn hearing performed with oto acoustic emissions (OAE) and auditory brain stem responses (ABR), in high-risk infants aged below 7 days, 15 days, after 45 days and after 90 days.</p><p><strong>Results: </strong>Study population comprised of 45 high-risk newborns. In 1^st level screening, 28 (62%) babies showed recordable OAE, 17 (38%) babies failed. In 2^nd level screening 31 (81%) passed and 7 (19%) failed and death occurred in 7 infants. In 3^rd level screening both OAE and brain stem evoked response audiometry (BERA), was performed in 38 cases and positivity was reported in 37 cases. 4^th level screening was similar to 3^rd level screening where 3 babies failed ABR test. In our study incidence of sensorineural hearing loss found to be 78.91% (3/38×1000) per 1000 high-risk babies. Auditory neuropathy was observed in 2 (4.4%) patients. Sensitivity and specificity of OAE was 100% and 33.3% respectively. In high-risk low birth weight neonates’ sensitivity and specificity was 66.7% and 50.0%.</p><p><strong>Conclusions: </strong>In high-risk babies, appropriate time for screening with OAE is around 60 days of age. OAE are useful diagnostic tool in evaluation of high-risk neonates for early detection of sensorineural hearing loss.</p>

The Controversial Role of Folic Acid on Diabetic Auditory Neuropathy

PurposeDiabetic auditory neuropathy(DAN) is a common complication of diabetes that seriously affects the quality of life in patients. In this study, we investigate the role of folic acid in the treatment of DAN in an experimental rat model.MethodsThirty-two Sprague-Dawley rats were equally divided into 4 groups: group 1, normal; group 2, diabetic rats; group 3and 4, rats treated with folic acid (40 and 80 mg/kg, respectively). The tools we used in this study to investigate the effect of folic acid on DAN were auditory brain stem response, stereology methodfor estimation ofthe volume and number ofspiral ganglion,volume of stria vascularis, and spiral ligament, and measurement of homocysteine (HCY), malondealdehyde(MDA) and superoxide dismutase.ResultsOur study showed that folic acid treatment was not significantly effective in improving structural and functional disorders in DAN, despite its effect in reducing HCY and MDA as oxidative biomarkers.ConclusionFolic acid is not effective in relieving morphological and functional disorders in DAN.

Effectiveness of Channel-Free Hearing Aid and Noise Desensitisation Training in Auditory Neuropathy Spectrum Disorder - Single Case Study

Auditory Neuropathy Spectrum Disorder is a rare condition wherein neural transmission through the VIIIth nerve and auditory brainstem is disrupted with intact peripheral hearing. Most frequently reported symptoms by individuals suffering from such conditions include impaired speech discrimination especially in presence of background noise. The aim of this single case study is to emphasize the effectiveness of channel-free technology as a rehabilitative option and to demonstrate the improvement in speech perception in noise with noise desensitisation training. A 24-year-old male patient reported to the National Institute of Speech and Hearing with the complaint of poor speech comprehension. The audiological profile revealed, bilateral moderate sensorineural hearing loss in pure tone audiometry with poor speech discrimination scores, bilateral ‘A’ type tympanogram with absent acoustic reflexes, good signal to noise ratio in otoacoustic emissions, and absent Auditory Brainstem Response at 95 dBnHL bilaterally suggestive of auditory neuropathy spectrum disorder in both the ears. As a part of rehabilitation, hearing aids with multiple channels and channel-free technology were tried and better speech discrimination scores were obtained with channel-free technology. In order to address poor speech discrimination in presence of noise, noise desensitisation training was given at different Signal to Noise Ratio with channel-free hearing aids and was found to be effective in improving the speech discrimination scores especially in adverse listening conditions. Key words: Auditory neuropathy spectrum disorder, Channel free hearing aid, Noise desensitisation.