Featured Research

from universities, journals, and other organizations

Molecular process behind form of non-syndromic deafness identified

Date:
August 27, 2013
Source:
Cincinnati Children's Hospital Medical Center
Summary:
Researchers identify an underlying molecular process that causes a genetic form of non-syndromic deafness in a new study that also suggests affected families may be at risk of damage to other organs.

Microscopic images from the study in the Journal of Clinical Investigation give a close up view of the degeneration of cochlear hair cells in mouse models of DFNB49 non-syndromic hearing loss. The top image shows almost normal hair formation at 12 days following birth, although the lower image shows severe degeneration setting in by day 16.
Credit: Image courtesy of Cincinnati Children's Hospital Medical Center

Researchers identify an underlying molecular process that causes a genetic form of non-syndromic deafness in a new study that also suggests affected families may be at risk of damage to other organs.

A multi-national research team led by scientists at Cincinnati Children's Hospital Medical Center report their findings in a study posted online Aug. 27 by the Journal of Clinical Investigation. The research opens the door to finding possible treatments for the condition (called DFNB49 non-syndromic hearing loss) and points to possible cellular damage in other organs like the heart, thyroid and salivary glands.

"Understanding the function of a deafness-causing mutation and the mechanism of disease progression is an important first step towards finding a therapeutic solution," said Saima Riazuddin, PhD, senior investigator and a scientist in the Division of Otolaryngology/Head and Neck Surgery at Cincinnati Children's. "But our study on mice also suggests we should clinically evaluate affected individuals more thoroughly, as they may have some other and not very obvious clinical problems involving multiple organs."

DFNB49 non-syndromic deafness is an inherited condition caused by mutations in the gene TRIC. Its "non-syndromic" designation means the hearing loss has not previously been linked to any other medical conditions.

To conduct their study, the researchers developed a first-ever "knock-in" mouse model of DFNB49 deafness by inserting mutations in the corresponding mouse version of the TRIC gene, known as Tric. This led to the loss of a critical protein called tricellulin in the mice.

Researchers report that loss of tricellulin disrupted the structure of what are called tight junctions in the epithelial cells of the cochlea in the inner ear. The authors suggest this affected the permeability of inner ear epithelia tissue, creating a possible channel that caused an imbalance in the quantity of ions and macromolecules. Researchers theorize this resulted in a detrimental environment and loss of cochlear hair cells, leading to hearing loss in the mice.

But the researchers also observed other unexpected characteristics in their newly generated Tric-mutated mice -- potentially harmful alterations in the cellular structures of salivary glands, thyroid glands and in heart cells. The animals also had enlarged hearts, livers, spleens and kidneys.

In particular, the scientists pointed to enlarged nuclei in the cardiomyocyte cells of mice, suggesting the possibility that the gene mutation in mice is linked to myocardial hypertrophy in the animals -- a dangerous thickening of the heart muscle.

The researchers stressed the need for additional research into their findings but cautioned against the immediate interpretation of data involving mouse models for treatment of human patients. Still, they suggest consideration of their findings is advisable in clinical follow-up of people with DFNB49.

"In previous studies, affected members of DFNB49 families did not reveal any other obvious conditions besides hearing loss, but the human families were not assessed to the same extent as the evaluation we conducted on the tricellulin mutant mice," said Riazuddin. "In light of our current findings, we are beginning to understand the broader function of tricellulin, and this study will guide us for further follow-up clinical evaluations of affected families to help us understand their complete medical spectrum."

Gowri Nayak, PhD, a research fellow at Cincinnati Children's (Pediatric Otolaryngology), led the study as a first author, under the guidance of Riazuddin (also an assistant professor of Pediatrics at the University of Cincinnati College of Medicine). Other collaborators included researchers from the National Institute on Deafness and other Communication Disorders, the National Heart, Lung and Blood Institute, the University of Kentucky (Department of Physiology), the University of Punjab in Lahore, Pakistan (National Center of Excellence in Microbiology), the University of Nebraska (Department of Special Education and Hearing Disorders) and University College of London in the United Kingdom (Centre for Auditory Research).

Funding support for the research came from the Deafness Research Foundation, Action on Hearing Loss, the National Institute on Deafness and other Communication Disorders (R01DC011748, DC011803, R01DC006443, R01DC009434, DC000039-15) and the International Center for Genetic Engineering and Biotechnology in Italy.


Story Source:

The above story is based on materials provided by Cincinnati Children's Hospital Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Gowri Nayak, Sue I. Lee, Rizwan Yousaf, Stephanie E. Edelmann, Claire Trincot, Christina M. Van Itallie, Ghanshyam P. Sinha, Maria Rafeeq, Sherri M. Jones, Inna A. Belyantseva, James M. Anderson, Andrew Forge, Gregory I. Frolenkov, Saima Riazuddin. Tricellulin deficiency affects tight junction architecture and cochlear hair cells. Journal of Clinical Investigation, 2013; DOI: 10.1172/JCI69031

Cite This Page:

Cincinnati Children's Hospital Medical Center. "Molecular process behind form of non-syndromic deafness identified." ScienceDaily. ScienceDaily, 27 August 2013. <www.sciencedaily.com/releases/2013/08/130827122812.htm>.
Cincinnati Children's Hospital Medical Center. (2013, August 27). Molecular process behind form of non-syndromic deafness identified. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2013/08/130827122812.htm
Cincinnati Children's Hospital Medical Center. "Molecular process behind form of non-syndromic deafness identified." ScienceDaily. www.sciencedaily.com/releases/2013/08/130827122812.htm (accessed August 22, 2014).

Share This




More Health & Medicine News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Two US Ebola Patients Leave Hospital Free of the Disease

Two US Ebola Patients Leave Hospital Free of the Disease

AFP (Aug. 21, 2014) Two American missionaries who were sickened with Ebola while working in Liberia and were treated with an experimental drug are doing better and have left the hospital, doctors say on August 21, 2014. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins