Preimplantation Genetic Diagnosis in Hereditary Hearing Impairment

Sensorineural hearing impairment is a common sensory deficit in children and more than 50% of these cases are caused by genetic etiologies, that is, hereditary hearing impairment (HHI). Recent advances in genomic medicine have revolutionized the diagnostics of, and counseling for, HHI, including preimplantation genetic diagnosis (PGD), thus providing parents-to-be with better reproductive choices. Over the past decade, we have performed PGD using the amplification refractory mutation system quantitative polymerase chain reaction (ARMS-qPCR) technique in 11 couples with a history of HHI, namely eight with GJB2 variants, one with OTOF variants, one with SLC26A4 variants, and one with an MITF variant. We demonstrated that PGD can be successfully applied to HHI of different inheritance modes, namely autosomal dominant or recessive, and phenotypes, namely syndromic or non-syndromic HHI. However, certain ethical concerns warrant scrutiny before PGD can be widely applied to at-risk couples with a history of HHI.

Speech production accuracy of children with auditory brainstem implants: A comparison with peers with cochlear implants and typical hearing using Levenshtein Distance

Auditory brainstem implantation (ABI) is a recent innovation in pediatric hearing restoration in children with a sensorineural hearing impairment. Only limited information is available on the spontaneous speech development of severe-to-profound congenitally hearing-impaired children who received an ABI. The purpose of this study was to investigate longitudinally the accuracy of ABI children’s word productions in spontaneous speech in comparison to the accuracy of children who received a cochlear implant and children with normal hearing. The data of this study consist of recordings of the spontaneous speech of the first three Dutch-speaking children living in Belgium who received an ABI. The children’s utterances were phonemically transcribed and for each word, the distance between the child’s production and the standard adult phonemic transcription was computed using the Levenshtein Distance as a metric. The same procedure was applied to the longitudinal data of the children with CI and the normally hearing children. The main result was that the Levenshtein Distance decreased in the three children with ABI but it remained significantly higher than that of children with typical hearing and cochlear implants matched on chronological age, hearing age, and lexicon size. In other words, the phonemic accuracy increased in the children with ABI but stayed well below that of children without hearing loss and children with cochlear implants. Moreover, the analyses revealed considerable individual variation between the children with ABI.

Downregulation of GJB2 and SLC26A4 Genes Induced by Noise Exposure is Associated with Cochlear Damage

Noise can change the pattern of gene expression inducing sensorineural hearing impairment. There is no investigation on effects of noise frequency on the expression of GJB2 and SLC26A4 genes involved in congenital hearing impairment in cochlear tissue. This study investigated impacts of white and purple noise on gene expression and pathologic changes of cochlear tissue. In this study, 32 adult male Westar rats were selected and divided into experimental groups WN (animals exposed to white noise with a frequency range of 100-20000 Hz), PN (animals exposed to purple noise with a frequency range of 4-20 kHz) and control groups. All experimental groups were exposed to a sound pressure level of 118-120 dB for 8 hours per day. Cochlear tissue sampling was performed for tissue pathology studies, also RNA was extracted at 1 hour & 1 week after cessation of noise exposure. The results showed that Both white and purple noises caused permanent damage to the cortical, estrosilica systems of hair cells and ganglion of the hearing nerve. GJB2 and SLC26A4 were downregulated in both groups exposed with white and purple noise. However, differences are notably more significant in 1 weak post-exposure than 1 hour. Our Findings suggest GJB2 and SLC26A4 can be considered as biomarkers of response to noise frequency which is associated with the pathological response of cochlear tissue, leading to sensorineural hearing impairment. It would be suggested the demand for a more conventional approach to assessment of noise-induced hearing loss and subsequently the practice of hearing protection programs.

A Hospital based study on sudden sensorineural Hearing Loss: It’s audiological characteristics and prevalence

Objectives: To analyze the prevalence & characteristics of sudden sensorineural hearing loss. Methods: This cross sectional study including n=377 cases of sensorineural hearing impairment, using non-probability convenience sampling, who fulfilled the selection criteria was conducted from 1st July 2019 to 31st October 2019. Study was conducted at Audiology section of ENT department, Lahore General Hospital, Pakistan. Sample included both genders, aged 17-70 years. Cases suffering from inflammatory or obstructive conditions of the external or middle ear and those who could not undergo pure tone audiometry were excluded from the study. Following consent for inclusion in study, data was collected using basic demographic and medical history sheet followed by Audiometric evaluation. Statistical Software for Social Sciences Version 20.0 was used for data analysis. Results: The prevalence rate of sudden sensorineural hearing loss of 14(3.7%) being significantly more common in males 11(78%) than females 3(22%) (p=0.05) & age group 15-35 years (p=0.001). It is commonly of severe or profound degree with downward sloping audiogram (p<0.05), however it is not associated with vertigo (p=0.32), tinnitus (p=0.08) with no side predilection (p = 0.27). Conclusion: We conclude that the prevalence of SSNHL is 3.7% being significantly more prevalent in males and those aged15-25 years. It is mostly characterized by severe to profound degree of hearing loss with downward sloping audiogram with no associated vertigo, tinnitus and side predilection. doi: https://doi.org/10.12669/pjms.37.4.3851 How to cite this:Naz E, Saqulain G, Mumtaz N, Babur MN. A Hospital based study on sudden sensorineural Hearing Loss: It’s audiological characteristics and prevalence. Pak J Med Sci. 2021;37(4):1133-1138. doi: https://doi.org/10.12669/pjms.37.4.3851 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

A novel variant in DXML2 gene is associated with autosomal dominant non-syndromic hearing impairment (DFNA71) in a Cameroonian family

Approximately half of congenital hearing impairment cases are inherited, with non-syndromic hearing impairment (NSHI) being the most frequent clinical entity of genetic hearing impairment cases. A family from Cameroon with NSHI was investigated by performing exome sequencing using DNA samples obtained from three family members, followed by direct Sanger sequencing in additional family members and controls participants. We identified an autosomal dominantly inherited novel missense variant [NM_001174116.2:c.918G>T; p.(Q306H)] in DMXL2 gene (MIM:612186) that co-segregates with mild to profound non-syndromic sensorineural hearing impairment . The p.(Q306H) variant which substitutes a highly conserved glutamine residue is predicted deleterious by various bioinformatics tools and is absent from several genome databases. This variant was also neither found in 121 apparently healthy controls without a family history of hearing impairment , nor 112 sporadic NSHI cases from Cameroon. There is one previous report of a large Han Chinese NSHI family that segregates a missense variant in DMXL2. The present study provides additional evidence that DMXL2 is involved in hearing impairment etiology, and we suggest DMXL2 should be considered in diagnostic hearing impairment panels.