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SUMMARY OF THE ARTICLE
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SUMMARY OF THE ARTICLE
First article:
Angeli, Lin and Liu (2012), conducted a review on the genes as well as a genetic
disorder that negatively impacted the hearing of the human and a few specific mouse models.
The researchers suggested that genes play a crucial role in the practice of medicine for gathering
an in-depth understanding of the biological process of genetic diseases. The researchers focused
on genes that code the proteins for hearing loss usually involved in the normal biological process
such as ear function, ionic channels, cochlear fluid homeostasis, stereo cilia morphology,
synaptic transmission, gene regulation and others. In this context, mouse models are the most
suitable experimental model that enable the understanding of the various genes associated with
pathogenesis. The result of the review suggested that a range of hearing loss has been identified
in recent years where genetic mutation plays a crucial role and most of these hearing losses are
monogenic disorders (Angeli, Lin and Liu 2012). The researchers suggested that monogenic
disorders are usually are classified into a range of categories where the gene for nonsyndromic
hearing loss is located in ~ 125 loci where 64 genes have been identified. The implication of this
research is that it will provide health professionals with a roadmap of designing interventions for
hear loss. The limitation of the research is that it is a literature review that requires primary
research.
Second article:
Géléoc and Holt (2014), conducted a literature review on the sound strategies for hearing
restoration. Hearing loss is considered as the common sensory deficit of human being that
impacted more than 300 million affected individuals worldwide. Environmental as we genetic
factors contributed to hearing loss that may result in the death of sensory cells. After conducting

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the review, researchers suggested that in order to restore hearing loss, the common strategies
include Cochlear Implants, gene therapy for genetic deafness, gene therapy for developed
deafness, and gene therapy for spiral ganglion neurons, stem cell therapies to generate of hair
cells and generation of auditory neurons and molecular therapies to generate new hair cells
(Géléoc and Holt 2014). On the other hand, genome editing is one of the most effective
approaches that could offer hope for restoration of hearing loss by restoring wild type sequence
of native DNA. As KCNQ4 mutation induces a dominant-progressive hearing loss amongst
human, implementation of these strategies may require significant overexpression of the wild-
type protein. The implication of the practice is that it will enable health care professionals to
recommend molecular and gene therapies for restoring hearing loss.
Third article:
Mizutari et al. (2013), conducted an experimental study on the notch signalling pathway
that induced regeneration of cochlear hair cell as well as recovery of hearing after severe trauma.
The researchers manipulated the notch signalling pathway for generating new hair cells in a
deafened animal. Moreover, researchers conducted research by identifying a potent γ-secretase
inhibitor by an assay of stem cells. They used a lineage tag for determining the source of the new
hair cells. The result of the study suggested that new hair cells can be produced and it can cause
fractional recovery of hearing which was damaged by severe noise. The underlying mechanism
is that when notch singling pathway is inhibited by y a γsecretase inhibitor chosen for
stimulating the differential of hair cells from inner stem cells, the generation resulted in
overexpression of the bHLH transcription factor, Atoh1 and inhibit the Notch pathway.
Consequently, notch pathway inhibition resulted in cochlear hair cell generation and restoration

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of hearing loss by noise trauma. Thus, influencing the fate of cell by pharmacological inhibition
of notch signalling pathway can be a therapeutic approach to treat deafness.
Fourth article:
Mittal et al. (2017) conducted a literature review on the recent advancement in the
regeneration of auditory hair cells as well restoration of hearing. Specialized neuroepithelial
sensory cells mediate neurosensory responses of hearing as well as balance through receptors.
Any disturbance of the biochemical, as well as molecular pathways facilitating these responses,
can result in deficits such as severe hearing impairment along with vestibular dysfunction.
Hence, the hearing loss in a human being can be influenced by both genetic and environmental
factors where auditory function impairment is one of the most common instances of
neurosensory deficit that affect one in 500 new-borns. The researchers suggested that damages
of auditory sensory cells are irreversible and sufficient damages to the cells leads to permanent
damage. While a range of gene therapies and molecular therapies are effective in restoring the
deafness, Cochlear implants are considered as most successful implants that can re-establish the
hearing. However, it offers limited recovery in expenses of loss (Mittal et al. 2017). The
regeneration of mammalian auditory hair cells can be the most effective strategy to restore the
hearing. The implication of the practice is that it will enable health care professionals to
recommend molecular and gene therapies for restoring hearing loss.
Fifth article:
Bowl et al. (2017), conducted a cohort study on the genetic landscapes for auditory
dysfunction in human. The researchers conducted a hearing loss screening of 3006 mice knock
out screening as a part of International Mouse Phenotyping Consortium and for identifying the

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SUMMARY OF THE ARTICLE
auditory phenotyping ABR tests. For conducting statistical analysis, PhenStat’ package was
used where a mixed model approach and sex and phenotypes are fixed parameters for statistical
analysis. After statistical analysis, manual curation was conducted which highlighted a set of 67
mutants with hearing loss (Bowl et al. 2017). The findings suggested that 15 mutants out of
67 mutants were considered as hearing loss loci and 52 were not previously associated with
hearing loss. A significant number of these genes expressed in the inner ear and play a vital role
in various aspect of hair cells in the cochlea. Moreover, calculation suggested that approximately
450 genes associated with hearing function is carried by the human genome and more than 400
genetic syndromes accompanied by hearing loss (Bowl et al. 2017). Hence, these genes can
be a novel target for restoring hearing loss in human for preventing deafness. However, the
researchers were unable to assess the developmental mutation and different genetic context of
homozygous viable which further highlighting a need for future research.

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SUMMARY OF THE ARTICLE
References:
Angeli, S., Lin, X. and Liu, X.Z., 2012. Genetics of hearing and deafness. The Anatomical
Record: Advances in Integrative Anatomy and Evolutionary Biology, 295(11), pp.1812-1829.
Géléoc, G.S. and Holt, J.R., 2014. Sound strategies for hearing restoration. Science, 344(6184),
p.1241062.
Mizutari, K., Fujioka, M., Hosoya, M., Bramhall, N., Okano, H.J., Okano, H. and Edge, A.S.,
2013. Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after
acoustic trauma. Neuron, 77(1), pp.58-69.
Mittal, R., Nguyen, D., Patel, A.P., Debs, L.H., Mittal, J., Yan, D., Eshraghi, A.A., Van De
Water, T.R. and Liu, X.Z., 2017. Recent advancements in the regeneration of auditory hair cells
and hearing restoration. Frontiers in molecular neuroscience, 10, p.236.