Facilitate speech comprehension in hereditary hearing loss patients

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Family trees of the Chinese family (HN66) and the Korean family (SB162) that segregate the TMEM43-p variant. (Arg372Ter) in an autosomal dominant manner. Credit: Institute for Basic Science

Hearing loss is a disability that affects approximately 5% of the world’s population. Clinical determination of the exact site of injury is critical to choosing an appropriate treatment for hearing loss. For example, subjects with damage to sound conduction or mild damage to external hair cells would benefit from hearing aids, while those with significant damage to external or internal hair cells would benefit from cochlear implants. On the other hand, subjects with deficiencies in more central structures such as the cochlear nerve, brainstem, or brain do not benefit from hearing aids or cochlear implants. However, the role of cochlear glial cell deficiencies in hearing loss is less well known. Although connexin channels in cochlear glial cells are known to play an important role in mediating potassium flow to the cochlea, the molecular and cellular mechanism of connexin channels and their role in loss progressive hearing have not been studied extensively.

Auditory neuropathy spectrum disorder (ANSD) is a confusing hearing disorder where subjects can respond to sound but have difficulty discriminating in speech. Recently, a collaboration of researchers from the Center for Cognition & Sociality (IBS), Seoul National University Bundang Hospital, Mokpo National University, Central South University, and the University of Miami, identified an unknown deafness gene that causes this disease. The new gene, TMEM43, is found on chromosome 3 and is expressed primarily in glia-like support. (GLS) of the cochlea. They identified that the variant p. (Arg372Ter) from TMEM43 was inherited from two famous Asian families in South Korea and China who are known to suffer from ANSD.

To study this disease, the researchers used a with the defective gene TMEM43-p. (Arg372Ter). The researchers found that this mouse model presented the same progressive as human ANSD subjects. Another examination of these mice revealed that the GLS cell size was smaller in older mice compared to that of control mice. In addition, the TMEM43 protein was shown to interact with connexin channels (Cx26 and Cx30), which are known to regulate K + conductance in the cochlea. K + conductance was significantly affected in the mutant mouse. Based on the mechanistic ideas of the mouse model, the researchers performed cochlear implants on 3 patients with human ANSD, which resulted in the successful restoration of their speech discrimination.

Facilitate speech comprehension in hereditary hearing loss patients

Electrical recordings of cochlear glia-like support cell (GLS). The knock-in mouse (KI) with TMEM43-p variant. (Arg372Ter) presents an alteration of the GLS K + conductance. Gray; control mice, cyan; KI heterozygous mice, purple; homozygous KI mice. Credit: Institute for Basic Science

This study is notable for the fact that they identified a new deafness gene in humans, studied the underlying mechanism of the genetic variant found in human subjects using a and applied the result again to human patients with successful clinical outcomes. Therefore, this study provides a model platform on which the personalized model of hearing rehabilitation can be determined, emphasizing the importance of an approach based on precision medicine.

Facilitate speech comprehension in hereditary hearing loss patients

Schematic diagram illustrating the role of TMEM43 in cochlear GLS. The cochlear GLS with TMEM43-p. (Arg372Ter) (right) show a significantly decreased K + -mediated passive current conductance compared to their WT counterpart (left), and their ability to maintain cell volume is disturbed. Credit: Institute for Basic Science

Dr. Choi Byung Yoon stated that “we are delighted to add TMEM43 to the list of genes that cause deafness. It will greatly contribute to the accurate diagnosis and personalized treatment of deafness with a simple genetic test.” In addition, Director C. Justin Lee mentioned that “This study emphasizes the important role of glial cells in the cochlea. We are confident that further research will give hope to many patients suffering from this rare form of deafness “.

As a future follow-up study, researchers look forward to recruiting additional subjects with other variants of ANSD genes in order to provide more clinical information on this rare disease of deafness. Based on the fact that the TMEM43 protein contributes to K + conductance in cochlear glial cells, the researchers plan to continue their study on the role of the TMEM43 protein and ion channels in the brain.


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More information:
A nonsense variant TMEM43 leads to disruption of connexin-linked function and autosomal dominant auditory neuropathy spectrum disorder. PNAS, 2021.

Citation: Facilitate speech comprehension in patients with inherited hearing loss (2021, May 24) Retrieved May 24, 2021 from https://medicalxpress.com/news/2021-05-speech-comprehension-rare- inherited-loss.html

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