Causative Gene for Sensori-Neural Hearing Loss

What if we could find out what really causes sensori- neural hearing loss?  The more we know of its origin, the more information we can digest as to how to cure it. Better Hearing Institute (BHI) (2016) summarizes the prevalence of sensori-neural hearing loss in the US:gen2

  • 3 in 10 people over age 60 have hearing loss;
  • 1 in 6 baby boomers (ages 41-59), or 14.6%, have a hearing problem;
  • 1 in 14 Generation Xers (ages 29-40), or 7.4%, already have hearing loss;
  • At least 1.4 million children (18 or younger) have hearing problems;
  • It is estimated that 3 in 1,000 infants are born with serious to profound hearing loss.

Estimates of hearing loss worldwide are about .1% of the world population according to the World Health Organization

General Causative Research

Since this study is causative research it is necessary to take a few minutes and review this type of research.  Causative research is very closely related to the correlation coefficient, but looks more deeply into the relationship between two variables.  A strong correlation between two variables, for example, might imply a causative relationship but it does not prove causation.  In a correlation relationship the researcher is  seeking to find out if X is related to Y.  In a causation relationship, however, the researcher is not simply looking to find if gen3the variables are related but how they are related.    For example, in causation the researcher looks to find that the value of X increases the value of Y due to an upward change in the difference between variables M and Z and correlation would simply seek to find out if X nd Y are related to each other.  

While correlation does not necessarily suggest causation, correlation is easier for most of us to understand and calculate so we often only look at correlation and then, often in error, assume that variables with  high correlation are causative.  Tiongson (2009) summarizes the differences between these two measurements.  Simply stated the differences are as follows:

  • The correlative approach looks at the presence or absence of a relationship – if and when it does exist -and whether such a correlation is linear or non-linear.
  • The causative approach attempts to explain relationships between two or more variables and their underlying, intervening variables.  Causation presupposes that there is a relationship – a hypothetical, theoretical relationship – between the two variables and seeks to explain, not merely  describe, the movements between the two variables ultimately arriving at an answer to the question “Why?”.

So, as you review the study presented here consider that their research was not simply a correlation relationship of sensori-neural hearing loss and a gene, but a true causative relationship.

Quest for the Origins of Sensori-Neural Hearing Loss

In the past two decades, the quest for the origins of sensori-neural hearing loss has led to extensive worldwide research on the genetics of nonsyndromic hereditary deafness (NSHD).  This research has led to  the discovery of gen4about 100 genes that are essential for hearing.  Most forms of NSHD are associated with permanent hearing loss caused by damage to structures within the inner ear. The inner ear consists of three parts: a snail-shaped structure called the cochlea that helps process sound, nerves that send information from the cochlea to the brain, and structures involved with balance. Loss of hearing caused by changes in the inner ear is called sensorineural deafness.   Thus, nonsyndromic hereditary deafness is usually sensori-neural. 

There are a number of studies that suggest there are about 30 of these 100 genes essential for hearing that encode proteins interacting directly or indirectly with actin.  Inside the cochlea, there are stereocilia (often called the Hair Cells (HC)) which are deflected by sound stimulation.  These actin based protrusion structures are essential for hearing.  Cochlear HCs are arranged in a single row of inner HCs called Inner Hair Cells (IHC) and three rows ofgen6 outer HCs (OHCs).  Although IHCs and OHCs are believed to share common mechanotransduction machinery, they have distinct roles during sound detection: IHCs are true sensors, whereas OHCs function as amplifiers through an active process that involves stereociliary and somatic motility.  The high sensitivity of HCs depends on the coordinated/synchronized movement of the stereocilia upon mechanical stimulation:  Thus, the precise organization of the length and shape of the stereocilia, which is regulated by a large battery of genes, is indispensable. 


Cooperative research between Kobe University and Kyoto University in Japan may have begun this quest for the origins of sensori-neural hearing loss. A causative gene for sensori-neural hearing loss has been identified by a group of Japanese researchers, genwho successfully replicated the condition using a transgenic mouse.  This discovery could potentially be used to develop new treatments for hearing loss. Leaders of the study, Dr. Takehiko Ueyama and Dr. Shin-icho Kitajiri and their teams.  In previous research, scientists discovered about 100 causative genes for sensorineural hearing loss.  However, there are many unexplained aspects to the process, such as the type of mutation occurring in these genes, and how this causes hearing impairment.  This time the research team identified the causative gene for autosomal dominant non-syndromic sensorineural deafness, DFNA1.  The causative gene for this disease was first suggested in 1997, but doubts were cast regarding it universality and properties. The research group carried out an exon analysis using next generation sequencing targeting 1123 Japanese patients that had sensori-neural hearing losses of unknown causes.In two families the Ueyama group found a novel mutation in the make up of the DIA 1 molecule (DIAPH1), which is involved in lengthening the linear actin filaments.  These filaments play an important role in the formation and maintenance of inner ear hair cells.  They used a biochemical gen7and biological analysis on  molecular level to prove that the DIA1 mutant protein was an active form variant that lengthens actin filaments even without external stimulation. For further study, the team also engineered a transgenic mouse that manifests this DIA1 mutant protein.  They have confirmed that the mouse exhibits the traits of sensori-neural hearing loss and, since it demonstrates progressive deafness less loss when young and more loss when old.  Electron microscope images ofgen1 the cochlear hair cells of the transgenic mice (TG) demonstrate progressive hearing loss.  At 5 weeks there is no difference between TG mice and control mice, but by 10 and 25 weeks there is aa drop off of advancing significantly: outer hair cells (red circles) and inner hair cells (white circles).  The study of these mutant mice could be the key for discovering treatment for acquired sensori-neural hearing loss. 


Better Hearing Institute (2016).  Prevalence of hearing loss.  Retrieved October 11, 2016.

Toingson, P.  (2009).  Causative and correlative research – which one is for you?  Marginally Subversive.  Retrieved October 11, 2016.

Ueyama, T., Ninoyu, Y., Nishio, S., Miyoshi, T., Torii, H., Nishimura, N., Sugahara, K., Sakata, H., Thumkeo, D., Sakaguchi, H., Watanabe, N., Usami, S., Saito, N., Kitajiri, S., (2016).  Constitutive activation of DIA 1 (DIAPH1) via terminal truncation causes human sensorineural hearing loss.  Embo Molecular Medicine.  Retrieved October 11, 2016.


Fitzackerly, J. (2015).  2015 hearing and balance.  University of Minnesota Medical School.  Retrieved October 12, 2016. (2016). Sensorineural hearing loss hearing aids.  Retrieved October 12, 2016.

About Robert Traynor

Robert M. Traynor is a board certified audiologist with 45 years of clinical practice in audiology. He is a hearing industry consultant, trainer, professor, conference speaker, practice manager, and author. He has 45 years experience teaching courses and training clinicians within the field of audiology with specific emphasis in hearing and tinnitus rehabilitation. Currently, he is an adjunct professor in various university audiology programs.


  1. Thanks for that, most interesting. I have been in contact with Dr Rachel Burt here in Australia, who’s studying the genetics of juvenile onset hearing loss (the GjB2 gene).

    I offered my dna for testing but no research is being done locally on adult onset. I understand testing is expensive.

    And as a side note, I recently interviewed someone a deaf dog rescue group. They tell me deafness in dogs is a recessive trait in white haired animals.

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