New Research: Scientists Identify Otosclerosis Gene

Researchers say they’ve pinpointed the first gene linked to otosclerosis, a common cause of hearing loss in adults that impacts three million Americans.

A team from Canada’s Memorial University and Western University identified the causative gene, called FOXL1. The study was published in Human Genetics and signals that there’s hope for earlier diagnosis and better treatment in the future.

Why otosclerosis causes hearing loss

Patients with otosclerosis have tiny bones (stapes) in the middle ear that can’t vibrate as they usually do. Hearing loss results, as the bones can’t conduct sound waves to the inner ear.

Right now, there’s no cure for otosclerosis, which tends to get worse over time. Many people who have it use hearing aids or have surgery to insert a prosthetic device in the ear, which can conduct sound vibrations to the inner ear.

Understanding the genetics of otosclerosis

The new study set out to learn more about the condition. They knew that otosclerosis can be inherited from one parent, so researchers only had to locate a single gene mutation and not a pair.

The team used gene mapping and newer sequencing techniques to isolate DNA, which was then analyzed. The mutation responsible, experts say, occurs in the FOXL1 gene.

A few years back, scientists looked at variants in SERPINF1, but couldn’t validate the discovery in later research.

“Discovering a gene responsible for otosclerosis will help us to understand the biology of this bone disease, and will pave the way to finding new drugs and therapies and possibly even prevent otosclerosis,” said Susan G. Stanton, PhD, an associate professor at Western University in Ontario, in a statement.

How the otosclerosis gene was identified

The team identified the FOXL1 gene mutation in a large family from Newfoundland in eastern Canada. They also included an unrelated group of patients from a different area of central Canada. One of the unrelated patients with a family history of otosclerosis carried the identical mutation in the same FOXL1 gene, the authors pointed out.

In the case of the Newfoundland family, the team provided a simple genetic test to identify who is at risk and who is not at risk of developing otosclerosis.

A genetic test means that doctors can confirm otosclerosis. Family members of those with the condition could also take a test to see if they have it.

Why this discovery matters

“Having a genetic test means that otosclerosis could be confirmed in those with a genetic defect, even before their hearing declines significantly, which could be important as new treatments become available,” Stanton explained.

Another researcher, Terry-Lynn Young, PhD, a professor at Memorial University, shared another viewpoint on why this research is so valuable. “This may be beneficial for younger family members who may be early in otosclerotic progression or may not yet exhibit any hearing loss. Even if there is no immediate treatment, it can be helpful to know why you (and your extended family) are having hearing problems and how important it is to protect your ears from further environmental damage, such as excessive noise exposure for example.”

Taking a step towards a cure?

With more information about specific genes that trigger bone growth in the ear, therapeutics could be developed to suppress the expression of these triggers and stop otosclerosis from progressing. Researchers also hope that, as pharmacological treatments advance, treatments can be targeted towards the specific gene or genes, or a pathway or pathways that cause the disease.

What’s more, “we want to look at what percentage of all otosclerosis cases are caused by FOXL1, and identify new OTSC genes,” Young told HearingTracker. (Scientists commonly refer to unidentified otosclerosis genes as “OTSC genes”.)

At least 50 percent of otosclerosis cases appear to be sporadic, meaning that they don’t run in families, and further research could unravel the mystery of what causes this—and potentially alleviate the issue.

“We are interested in looking at the role of the OTSC genes in sporadic cases and their interplay with potential environmental factors. Discovery of all OTSC genes is critical to understanding the genetic architecture of otosclerosis,” Young added.

The researchers are also interested in taking a closer look at the natural course of FOXL1-associated otosclerosis, including its average age of onset and progression of clinical hearing loss, Young said.

What we know, what we don’t

Not everyone is so sure of the positive impact of this research.

“While interesting, the discovery really has no immediate impact whatsoever for clinicians evaluating and treating patients with otosclerosis,” noted David J. Eisenman, MD, an associate professor and vice chairman of the Department of Otorhinolaryngology at the University of Maryland School of Medicine. He was not part of the research.

“The primary symptom of otosclerosis, the one that makes people seek treatment in the vast majority of cases, is hearing loss,” he told HearingTracker. Having a hearing test is a more accurate and less expensive way to detect early hearing loss compared to a genetic test. “Since treatment wouldn't be indicated unless there was hearing loss, early genetic testing won't change anything.”

Also, the discovery only pertained to the families studied, and other factors may be involved in this kind of hearing loss. “The genetics of otosclerosis are complex and it is likely that it involves different genes in different people and probably some environmental factors as well. This is another piece of the puzzle,” said Michael J. Ruckenstein, MD, a professor at University of Pennsylvania Health System and co-director of the Center for Adult Onset Hearing Loss, in an email to HearingTracker.

Looking ahead

Young pointed out that the FOXL1 gene discovery provides “the first real glimpse into pathways that trigger new bone growth in the inner ear.”

Given that FOXL1 is only one of 10 OTSC genes that have been mapped in the human genome, her team hopes their research “leads to a cascade of OTSC gene discoveries.”

“Through genetics, new targeted therapies will be available to intervene and treat otosclerosis, likely within this decade,” Young said. “Developing new treatments that prevent or cure otosclerosis is the ultimate goal.”

Whether or not that timeline holds, Eisenman said it’s good to see research on the genetic components of hearing disorders. People should recognize that hearing loss is an urgent topic if researchers are looking at it from many different angles.